Signaling pathways In D1R containing striatal spiny projection neurons (Blackwell et al 2018)

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Accession:239744
We implemented a mechanistic model of signaling pathways activated by dopamine D1 receptors, acetylcholine receptors, and glutamate. We use our novel, computationally efficient simulator, NeuroRD, to simulate stochastic interactions both within and between dendritic spines. Results show that the combined activity of several key plasticity molecules correctly predicts the occurrence of either LTP, LTD or no plasticity for numerous experimental protocols.
Reference:
1 . Blackwell KT, Salinas AG, Tewatia P, English B, Hellgren Kotaleski J, Lovinger DM (2019) Molecular mechanisms underlying striatal synaptic plasticity: relevance to chronic alcohol consumption and seeking. Eur J Neurosci 49:768-783 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Molecular Network; Synapse;
Brain Region(s)/Organism: Basal ganglia; Striatum;
Cell Type(s): Neostriatum medium spiny direct pathway GABA cell;
Channel(s):
Gap Junctions:
Receptor(s): D1; mGluR5; M1; M4;
Gene(s):
Transmitter(s): Acetylcholine; Dopamine; Endocannabinoid; Glutamate;
Simulation Environment: NeuroRD;
Model Concept(s): G-protein coupled; Long-term Synaptic Plasticity; Signaling pathways; Alcohol Use Disorder;
Implementer(s): Blackwell, Avrama [avrama at gmu.edu];
Search NeuronDB for information about:  Neostriatum medium spiny direct pathway GABA cell; M1; M4; mGluR5; D1; Acetylcholine; Dopamine; Glutamate; Endocannabinoid;
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Stim_CaBathOA.xml
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Stim20hzACh-sp2adj.xml
Stim20hzACh-sp2other.xml
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Stim20hzACh-sp3sep.xml
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StimCouple20hz_DaDelay-10sITI.xml
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StimCouple20hzAChNoDa-10sITI.xml
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StimCoupleTheta10hz_m4block-15sITI.xml
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StimCoupleTheta10hzAChNoDa-15sITI.xml
StimCoupleTheta10hzAChNoDip-15sITI.xml
StimCoupleTheta10hzAChNoGlu-15sITI.xml
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StimCoupleTheta10hzAChNoRebound_DaDec1-15sITI_onset50.xml
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StimDend_DaBath.xml
StimDend_DaCaBath.xml
StimTheta10hzACh-sp1.xml
StimTheta10hzACh-sp2adj.xml
StimTheta10hzACh-sp2other.xml
StimTheta10hzACh-sp2sep.xml
StimTheta10hzACh-sp3sep.xml
                            
<ReactionScheme>
  <!-- Merged, tuned model, with CamKII phos of DagL.
       Uses higher order reactions for CamKII phosphorylation -->
<!-- calcium stuff first -->
    <Specie name="Ca"             id="Ca"            kdiff="174.3" kdiffunit="mu2/s"/>
    <Specie name="CaOut"          id="CaOut"         kdiff="174.3" kdiffunit="mu2/s"/>
    <Specie name="CaOutLeak"      id="CaOutLeak"     kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="Leak"           id="Leak"          kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="Calbin"         id="Calbin"        kdiff="9.3"   kdiffunit="mu2/s"/>
    <Specie name="CalbinC"        id="CalbinC"       kdiff="9.3"   kdiffunit="mu2/s"/>
    <Specie name="pmca"           id="pmca"          kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="ncx"            id="ncx"           kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="pmcaCa"         id="pmcaCa"        kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="ncxCa"          id="ncxCa"         kdiff="0"     kdiffunit="mu2/s"/>

<!-- CaM from Gq files, with either C or N site binding first -->
    <Specie name="Cam"            id="Cam"           kdiff="11"    kdiffunit="mu2/s"/>
    <Specie name="CamCa2C"        id="CamCa2C"       kdiff="11"    kdiffunit="mu2/s"/>
    <Specie name="CamCa2N"        id="CamCa2N"       kdiff="11"    kdiffunit="mu2/s"/>
    <Specie name="CamCa4"         id="CamCa4"        kdiff="11"    kdiffunit="mu2/s"/>

<!-- Gs coupled Dopamine D1 Receptor; Ligand currently called L,
     Dbuf is used to eliminate injected D -->
    <Specie name="Da"            id="Da"            kdiff="10"     kdiffunit="mu2/s"/>
    <Specie name="Dbuf"          id="Dbuf"          kdiff="1"      kdiffunit="mu2/s"/>
    <Specie name="DaDbuf"        id="DaDbuf"        kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="DaOut"         id="DaOut"         kdiff="1"      kdiffunit = "mu2/s"/>
    <Specie name="D1R"           id="D1R"           kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="DaD1R"         id="DaD1R"         kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="Gsabg"         id="Gsabg"         kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="DaD1RGs"       id="DaD1RGs"       kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="GsD1R"         id="GsD1R"         kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PKAcDaD1RGs"   id="PKAcDaD1RGs"   kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="pDaD1RGs"      id="pDaD1RGs"      kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="pGsD1R"        id="pGsD1R"        kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="GsaGTP"        id="GsaGTP"        kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="GsaGDP"        id="GsaGDP"        kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="Gbg"           id="Gbg"           kdiff="0"     kdiffunit="mu2/s"/>

<!-- Gi coupled m4R -->
    <Specie name="ACh"          id="ACh"         kdiff="10"      kdiffunit = "mu2/s"/>
    <Specie name="m4R"         id="m4R"          kdiff="0"       kdiffunit = "mu2/s"/>
    <Specie name="AChm4R"       id="AChm4R"      kdiff="0"      kdiffunit = "mu2/s"/>
    <Specie name="Giabg"       id="Giabg"        kdiff="0"       kdiffunit = "mu2/s"/>
    <Specie name="AChm4RGi"     id="AChm4RGi"    kdiff="0"      kdiffunit = "mu2/s"/>
    <Specie name="Gim4R"       id="Gim4R"        kdiff="0"       kdiffunit = "mu2/s"/>
    <Specie name="GiaGTP"      id="GiaGTP"       kdiff="0"       kdiffunit = "mu2/s"/>
    <Specie name="GiaGDP"      id="GiaGDP"       kdiff="0"       kdiffunit = "mu2/s"/>
<!-- Gi coupled m4R -->
    <Specie name="m1R"          id="m1R"         kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="AChm1R"       id="AChm1R"      kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="m1RGq"        id="m1RGq"       kdiff="0"     kdiffunit="mu2/s"/> 
    <Specie name="AChm1RGq"     id="AChm1RGq"    kdiff="0"     kdiffunit="mu2/s"/>
<!--m1R or m4R inhibition -->
    <Specie name="telenz"       id="telenz"      kdiff="1"     kdiffunit="mu2/s"/>
    <Specie name="telenzm1R"    id="telenzm1R"   kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="telenzm1RGq"  id="telenzm1RGq" kdiff="0"     kdiffunit="mu2/s"/>

    <Specie name="PD1028"       id="PD1028"      kdiff="1"      kdiffunit = "mu2/s"/>
    <Specie name="PD1028m4R"    id="PD1028m4R"   kdiff="0"      kdiffunit = "mu2/s"/>
    <Specie name="PD1028m4RGi"  id="PD1028m4RGi" kdiff="0"      kdiffunit = "mu2/s"/>

    <!-- Gq coupled mGluR or mAChR receptor; ligand currently called Glu,
     GluOut is used to eliminate injected Glu -->
    <Specie name="Glu"            id="Glu"           kdiff="0.01"   kdiffunit="mu2/s"/>
    <Specie name="GluGbuf"        id="GluGbuf"       kdiff="0"    kdiffunit="mu2/s"/>
    <Specie name="GluOut"         id="GluOut"        kdiff="1"   kdiffunit="mu2/s"/>
    <Specie name="Gbuf"           id="Gbuf"          kdiff="1"     kdiffunit="mu2/s"/>
    <Specie name="MgluR"          id="MgluR"         kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="GluMgluR"       id="GluMgluR"      kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="GluMgluRdesens" id="GluMgluRdesens" kdiff="0"    kdiffunit="mu2/s"/>
    <Specie name="MgluRGq"        id="MgluRGq"       kdiff="0"     kdiffunit="mu2/s"/> 
    <Specie name="Gqabg"          id="Gqabg"         kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="GluMgluRGq"     id="GluMgluRGq"    kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="GqaGTP"         id="GqaGTP"        kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="GqaGDP"         id="GqaGDP"        kdiff="0"     kdiffunit="mu2/s"/>

<!-- This is AC5, from Gs model.  May need to add AC1 at some point -->
    <Specie name="AC5"             id="AC5"            kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="AC5Gsa"          id="AC5Gsa"         kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="AC5GsaATP"       id="AC5GsaATP"      kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="AC5Ca"           id="AC5Ca"          kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="AC5GsaCa"        id="AC5GsaCa"       kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="AC5GsaCaATP"     id="AC5GsaCaATP"    kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="AC5Gia"          id="AC5Gia"         kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="AC5GsaGia"       id="AC5GsaGia"      kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="AC5GsaGiaATP"    id="AC5GsaGiaATP"   kdiff="0"     kdiffunit="mu2/s"/>

    <Specie name="AC1" id="AC1" kdiff="0" kdiffunit="mu2/s"/>
    <Specie name="AC1Gsa" id="AC1Gsa" kdiff="0" kdiffunit="mu2/s"/>
    <Specie name="AC1GsaCamCa4" id="AC1GsaCamCa4" kdiff="0" kdiffunit="mu2/s"/>
    <Specie name="AC1GsaCamCa4ATP" id="AC1GsaCamCa4ATP" kdiff="0" kdiffunit="mu2/s"/>
    <Specie name="AC1CamCa4" id="AC1CamCa4" kdiff="0" kdiffunit="mu2/s"/>
    <Specie name="AC1CamCa4ATP" id="AC1CamCa4ATP" kdiff="0" kdiffunit="mu2/s"/>

    <!-- cAMP, and degradation by PDEs, from Gs model -->
    <!--Specie name="ATP"            id="ATP"           kdiff="74.8"  kdiffunit="mu2/s"/-->
    <Specie name="cAMP"           id="cAMP"          kdiff="86.4"  kdiffunit="mu2/s"/>
    <Specie name="AMP"            id="AMP"           kdiff="0"     kdiffunit="mu2/s"/>

    <Specie name="PDE1"           id="PDE1"          kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PDE1CamCa4cAMP" id="PDE1CamCa4cAMP" kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PDE1CamCa4"     id="PDE1CamCa4"    kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PDE10"          id="PDE10"         kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PDE10cAMP"      id="PDE10cAMP"     kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PKAcPDE10"      id="PKAcPDE10"     kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PKAcPDE10cAMP"  id="PKAcPDE10cAMP"  kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="pPDE10"         id="pPDE10"        kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="pPDE10cAMP"     id="pPDE10cAMP"    kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="pPDE10PP2A"      id="pPDE10PP2A"     kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="pPDE10PP2Ac"      id="pPDE10PP2Ac"     kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PDE2"           id="PDE2"          kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PDE2cAMP"       id="PDE2cAMP"      kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PDE2cAMP2"      id="PDE2cAMP2"     kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PDE4"         id="PDE4"      kdiff="6.01" kdiffunit="mu2/s"/>
    <Specie name="PDE4cAMP"     id="PDE4cAMP"  kdiff="6.0" kdiffunit="mu2/s"/>
    <Specie name="PKAcPDE4"     id="PKAcPDE4"  kdiff="5.4" kdiffunit="mu2/s"/>
    <Specie name="PKAcPDE4cAMP"  id="PKAcPDE4cAMP"  kdiff="5.41" kdiffunit="mu2/s"/>
    <Specie name="pPDE4"        id="pPDE4"     kdiff="6.01" kdiffunit="mu2/s"/>
    <Specie name="pPDE4PP2A"     id="pPDE4PP2A"     kdiff="6.61" kdiffunit="mu2/s"/>
    <Specie name="pPDE4PP2Ac"     id="pPDE4PP2Ac"     kdiff="6.61" kdiffunit="mu2/s"/>
    <Specie name="pPDE4cAMP"    id="pPDE4cAMP" kdiff="6.0" kdiffunit="mu2/s"/>

    <Specie name="Pap"          id="Pap"         kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PapPDE10"     id="PapPDE10"         kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="Roli"          id="Roli"         kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="RoliPDE4"      id="RoliPDE4"         kdiff="0"     kdiffunit="mu2/s"/>

    <!-- Gq, PLC, Dag, IP3, PKC and 2ag are from Gq model --> 
    <Specie name="Plc"            id="Plc"           kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PlcCa"          id="PlcCa"         kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PlcCaGqa"       id="PlcCaGqa"      kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PlcGqa"         id="PlcGqa"        kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="Pip2"           id="Pip2"          kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PlcCaPip2"      id="PlcCaPip2"     kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PlcCaGqaPip2"   id="PlcCaGqaPip2"  kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="Ip3"            id="Ip3"           kdiff="79.6"  kdiffunit="mu2/s"/>
    <Specie name="Dag"            id="Dag"           kdiff="0"     kdiffunit="mu2/s"/>

<!-- degradation of Dag, 2ag and IP3 -->
    <Specie name="DagK"           id="DagK"          kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="DagKdag"        id="DagKdag"       kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PA"             id="PA"            kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="2agDegrad"      id="2agDegrad"     kdiff="88.6"  kdiffunit="mu2/s"/>
    <Specie name="Ip3degrad"      id="Ip3degrad"     kdiff="79.6"  kdiffunit="mu2/s"/>
<!-- Production of endocannabinoid -->
    <Specie name="Dgl"            id="Dgl"           kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="pDgl"           id="pDgl"          kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="CaDgl"          id="CaDgl"         kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="CapDgl"          id="CapDgl"         kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="DagCaDgl"       id="DagCaDgl"      kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="DagCapDgl"       id="DagCapDgl"      kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="2ag"            id="2ag"           kdiff="88.6"  kdiffunit="mu2/s"/>
    <Specie name="Dgl_CKCamCa4"   id="Dgl_CKCamCa4"   kdiff="0"   kdiffunit="mu2/s"/>
    <Specie name="Dgl_CKpCamCa4"  id="Dgl_CKpCamCa4"  kdiff="0"   kdiffunit="mu2/s"/>
    <Specie name="CaDgl_CKCamCa4"   id="CaDgl_CKCamCa4"   kdiff="0"   kdiffunit="mu2/s"/>
    <Specie name="CaDgl_CKpCamCa4"  id="CaDgl_CKpCamCa4"  kdiff="0"   kdiffunit="mu2/s"/>
    <Specie name="Dgl_CKp"        id="Dgl_CKp"        kdiff="0"   kdiffunit="mu2/s"/>

<!-- Kinases and Phosphatases -->    
    <Specie name="PIkinase"       id="PIkinase"      kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="Ip3degPIk"      id="Ip3degPIk"     kdiff="0"     kdiffunit="mu2/s"/>
    
    <Specie name="Pkc"            id="Pkc"           kdiff="6.61"    kdiffunit="mu2/s"/>
    <Specie name="PkcCa"          id="PkcCa"         kdiff="6.61"    kdiffunit="mu2/s"/>
    <Specie name="PkcCaDag"       id="PkcCaDag"      kdiff="0"     kdiffunit="mu2/s"/>
   
<!-- PP1, PP2B, PP2A, CaMKII, PKA, Darpp32 from Gs, since Gq didn't have them -->     
<!-- PP1, PP2B, PP2A are non-diffusible? -->     
    <Specie name="PP2B"           id="PP2B"          kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PP2BCam"        id="PP2BCam"       kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PP2BCamCa2C"    id="PP2BCamCa2C"   kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PP2BCamCa2N"    id="PP2BCamCa2N"   kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PP2BCamCa4"     id="PP2BCamCa4"    kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PP1"            id="PP1"           kdiff="0"     kdiffunit="mu2/s"/>

<!-- PP2A -->
    <Specie name="PP2ABPR72"      id="PP2ABPR72"    kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PP2AB56d"       id="PP2AB56d"     kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PKAcPP2AB56d"   id="PKAcPP2AB56d" kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="pPP2A"          id="pPP2A"         kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PP2Acal"        id="PP2Acal"       kdiff="0"     kdiffunit="mu2/s"/>

<!-- CaMKII: delete Complex and pComplex and re-do rate  constants when using new NeuroRD version -->
    <Specie name="CK"             id="CK"            kdiff="3.6"   kdiffunit="mu2/s"/>
    <Specie name="CKCamCa4"       id="CKCamCa4"      kdiff="3.6"   kdiffunit="mu2/s"/>
    <Specie name="CKpCamCa4"      id="CKpCamCa4"     kdiff="3.6"   kdiffunit="mu2/s"/>
    <Specie name="CKp"            id="CKp"           kdiff="3.6"   kdiffunit="mu2/s"/>
    <Specie name="CKpPP1"         id="CKpPP1"        kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="CKpCamCa4PP1"   id="CKpCamCa4PP1"  kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="CKCam_block"    id="CKCam_block"   kdiff="0"   kdiffunit="mu2/s"/>
    <Specie name="AIP"            id="AIP"           kdiff="1"   kdiffunit="mu2/s"/>
        
    <!-- PKA -->
    <Specie name="PKA"            id="PKA"           kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PKAcAMP2"       id="PKAcAMP2"      kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PKAcAMP4"       id="PKAcAMP4"      kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PKAc"           id="PKAc"          kdiff="0.836" kdiffunit="mu2/s"/>
    <Specie name="PKAr"           id="PKAr"          kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="Epac1"          id="Epac1"         kdiff="10"    kdiffunit="mu2/s"/>
    <Specie name="Epac1cAMP"      id="Epac1cAMP"     kdiff="10"    kdiffunit="mu2/s"/>
<!-- Use the updated reactions from Asia's hippocampal model -->

<!-- D32,D32p34 -->
    <Specie name="D32"            id="D32"           kdiff="8.9"   kdiffunit="mu2/s"/>
    <Specie name="D32PKAc"         id="D32PKAc"        kdiff="6.8"   kdiffunit="mu2/s"/>
    <Specie name="D32p34"           id="D32p34"          kdiff="8.8"   kdiffunit="mu2/s"/>
    <Specie name="D32p34PP1"        id="D32p34PP1"       kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="D32p34PP2BCamCa4" id="D32p34PP2BCamCa4" kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="D32p34PP1PP2BCamCa4" id="D32p34PP1PP2BCamCa4" kdiff="0"  kdiffunit="mu2/s"/>
    <Specie name="D32p34PP1PP2BCamCa2C" id="D32p34PP1PP2BCamCa2C" kdiff="0"  kdiffunit="mu2/s"/>
    <Specie name="D32p34PP2ABPR72"  id="D32p34PP2ABPR72" kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="D32p34PP2AB56d"   id="D32p34PP2AB56d"  kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="D32p34PP1PP2ABPR72" id="D32p34PP1PP2ABPR72" kdiff="0"  kdiffunit="mu2/s"/>
    <Specie name="D32p34PP1PP2AB56d" id="D32p34PP1PP2AB56d"  kdiff="0"  kdiffunit="mu2/s"/>

<!-- D32p75 -->
    <Specie name="Cdk5"           id="Cdk5"          kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="Cdk5D32"        id="Cdk5D32"       kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="D32p75"           id="D32p75"          kdiff="8.8"   kdiffunit="mu2/s"/>
    <Specie name="D32p75PKAc"        id="D32p75PKAc"       kdiff="6.8"   kdiffunit="mu2/s"/>
    <Specie name="D32p75PP2ABPR72"  id="D32p75PP2ABPR72"  kdiff="0"   kdiffunit="mu2/s"/>
    <Specie name="D32p75PP2AB56d"   id="D32p75PP2AB56d"   kdiff="0"   kdiffunit="mu2/s"/>
    <Specie name="D32p75PP2Acal"      id="D32p75PP2Acal"     kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="D32p75pPP2A"      id="D32p75pPP2A"     kdiff="0"     kdiffunit="mu2/s"/>
<!-- AKAR -->
    <Specie name="AKAR3"        id="AKAR3"       kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="pAKAR3"       id="pAKAR3"      kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PKAcAKAR3"    id="PKAcAKAR3"     kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="PP1pAKAR3"    id="PP1pAKAR3"     kdiff="0"     kdiffunit="mu2/s"/>

    <!-- blockers -->
    <Specie name="OkadaicAcid"        id="OA"              kdiff="1"     kdiffunit="mu2/s"/>
    <Specie name="CyclosporinA"       id="CyA"             kdiff="1"     kdiffunit="mu2/s"/>
    <Specie name="OA_PP2ABPR72"       id="OA_PP2ABPR72"    kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="OA_PP2AB56d"        id="OA_PP2AB56d"     kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="OA_pPP2A"           id="OA_pPP2A"        kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="OA_PP2Acal"         id="OA_PP2Acal"      kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="OA_PP1"             id="OA_PP1"          kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="CyA_PP2B"           id="CyA_PP2B"        kdiff="0"     kdiffunit="mu2/s"/>
    <Specie name="CyA_PP2BCa2C"       id="CyA_PP2BCa2C"    kdiff="0"     kdiffunit="mu2/s"/>
   
<!-- For now, no GluA1 receptors -->

<!--*************************************************************************
    Now, the reactions themselves   SAME means params are same in both files
    **************************************************************************-->
<!--I. *********** Ca pump and buffer rxns  ************* -->
<!-- i: Ca pump high affinity -    Ca + pmca <-> pmcaCa  SAME-->
    <Reaction name = "Ca_pump1a" id="Ca_pump1a">
	<Reactant specieID="Ca"/>
	<Reactant specieID="pmca"/>
	<Product specieID="pmcaCa"/>

	<forwardRate>0.05e-3</forwardRate>
	<reverseRate>9e-3</reverseRate>
    </Reaction>

<!-- ii: Ca pump high affinity -    pmcaCa <-> pmca + CaOut   SAME-->
    <Reaction name = "Ca_pump1b" id="Ca_pump1b">
	<Reactant specieID="pmcaCa"/>
	<Product specieID="pmca"/>
	<Product specieID="CaOut"/>

	<forwardRate>3.0e-3</forwardRate>
	<reverseRate>0</reverseRate>
    </Reaction>

<!-- iii: Ca pump low affinity -    Ca + ncx <-> ncxCa  SAME-->
    <Reaction name = "Ca_pump2a" id="Ca_pump2a">
	<Reactant specieID="Ca"/>
	<Reactant specieID="ncx"/>
	<Product specieID="ncxCa"/>

	<forwardRate>0.011e-3</forwardRate>
	<reverseRate>11.2e-3</reverseRate>
    </Reaction>

<!-- iv: Ca pump low affinity -    ncxCa <-> ncx + CaOut   SAME-->
    <Reaction name = "Ca_pump2b" id="Ca_pump2b">
	<Reactant specieID="ncxCa"/>
	<Product specieID="ncx"/>
	<Product specieID="CaOut"/>

	<forwardRate>5.6e-3</forwardRate>
	<reverseRate>0</reverseRate>
    </Reaction>
<!-- v: Ca leak -    CaOut + Leak <-> CaOutLeak  GQ RXN FILE, Leak is sm only-->
    <Reaction name = "Ca_leak" id="Ca_leak">
	<Reactant specieID="CaOut"/>
	<Reactant specieID="Leak"/>
	<Product specieID="CaOutLeak"/>

        <forwardRate>0.01e-6</forwardRate>
	<reverseRate>1.1e-3</reverseRate>
    </Reaction>

<!-- vi: Ca leak -    CaOutLeak <-> Ca (inside) + Leak  -->
    <Reaction name = "Ca_leak" id="Ca_leak">
	<Reactant specieID="CaOutLeak"/>
	<Product specieID="Ca"/>
	<Product specieID="Leak"/>

        <forwardRate>1.1e-3</forwardRate>
	<reverseRate>0</reverseRate>
    </Reaction>

<!-- vii: Ca Buffer    Ca + Calbindin <-> calbinC  SAME-->
    <Reaction name = "Ca_buffer" id="Ca_Buffer">
        <Reactant specieID="Ca"/>
        <Reactant specieID="Calbin"/>
        <Product specieID="CalbinC"/>

        <forwardRate>0.028e-3</forwardRate>
        <reverseRate>19.6</reverseRate>
    </Reaction>

<!--1A) Cam  + 2Ca <-> CamCa2C GQ RXN FILE, C or N can bind first-->
    <Reaction name = "CamC_bind" id="CamC_bind">
	<Reactant specieID="Cam"/>
	<Reactant specieID="Ca" n="2"/>
	<Product specieID="CamCa2C"/>

	<forwardRate>0.006e-3</forwardRate>
	<reverseRate>9.1e-3</reverseRate>
    </Reaction>

<!--2A) CamCa2C  + 2Ca <-> CamCa4 GQ RXN FILE, C or N can bind first-->
    <Reaction name = "CamCa2C_bind" id="CamCa2C_bind">
	<Reactant specieID="CamCa2C"/>
	<Reactant specieID="Ca" n="2"/>
	<Product specieID="CamCa4"/>

	<forwardRate>0.1e-3</forwardRate>
	<reverseRate>1000e-3</reverseRate>
    </Reaction>

<!--1B) Cam  + 2Ca <-> CamCa2N GQ RXN FILE, C or N can bind first-->
    <Reaction name = "CamN_bind" id="CamN_bind">
	<Reactant specieID="Cam"/>
	<Reactant specieID="Ca" n="2"/>
	<Product specieID="CamCa2N"/>

	<forwardRate>0.1e-3</forwardRate>
	<reverseRate>1000e-3</reverseRate>
    </Reaction>

<!--2B) CamCa2N  + 2Ca <-> CamCa4 GQ RXN FILE, C or N can bind first-->
    <Reaction name = "CamCa2N_bind" id="CamCa2N_bind">
	<Reactant specieID="CamCa2N"/>
	<Reactant specieID="Ca" n="2"/>
	<Product specieID="CamCa4"/>

	<forwardRate>0.006e-3</forwardRate>
	<reverseRate>9.1e-3</reverseRate>
    </Reaction>

<!--II. *********** Gs coupled receptor, from GS RXN FILE *************-->
    <!--0a. Injected DaDbuf dissociates to Dbuf (external) and Da: DaDbuf -> Da + Dbuf  -->
    <Reaction name = "DaDbuf--Da+Dbuf" id="DaDbuf--Da+Dbuf">
        <Reactant specieID="DaDbuf"                      />
        <Product  specieID="Dbuf"                      />
        <Product  specieID="Da"                     />
        <forwardRate> 20e-03 </forwardRate>
        <reverseRate> 0      </reverseRate>
    </Reaction>
    
  <!--0b. Da or Da Agonist is extruded  -->
   <Reaction name = "Da--DaOut" id="Da--DaOut">
  	<Reactant specieID="Da"/>
        <Product  specieID="DaOut"                   />
        <forwardRate> 1.0e-3      </forwardRate>
        <reverseRate> 0.055e-6      </reverseRate>
    </Reaction>

   <!--0c. excess DaOut eliminated to prevent baseline shift: DaOut + Dbuf  <->  DaOutbuf  -->
    <Reaction name = "DaOut+Dbuf--NULL" id="DaOut_buf--NULL">
        <Reactant specieID="DaOut"                      />
        <Reactant specieID="Dbuf"                      />
        <forwardRate> 1e-06 </forwardRate>
        <reverseRate> 0      </reverseRate>
    </Reaction>
    
  <!--1a. Da + D1R        <-> DaD1R      Kd=3000  source: Sunahara et al. Nature 1991-->
    <Reaction name = "Da+D1R--DaD1R" id="Da+D1R--DaD1R">
        <Reactant specieID="Da"                      />
        <Reactant specieID="D1R"                      />
        <Product  specieID="DaD1R"                     />

        <forwardRate> 0.00166667e-03 </forwardRate>
        <reverseRate> 5e-03        </reverseRate>
    </Reaction>
   <!-- 2a. DaD1R + Gsabg     <-> DaD1RGs      Kd=11.666667   source: Zhuang J Neurosci 2000-->
    <Reaction name = "DaD1R+Gs--DaD1RGs" id="DaD1R+Gs--DaD1RGs">
        <Reactant specieID="DaD1R"                     />
        <Reactant specieID="Gsabg"                      />
        <Product  specieID="DaD1RGs"                    />

        <forwardRate> 0.03e-03 </forwardRate>
        <reverseRate> 0.4e-03  </reverseRate>
    </Reaction>
    <!-- 1b. Gsabg + D1R       <-> GsD1R         Kd=35   source: PMR-->
    <Reaction name = "Gsabg+D1R--GsD1R" id="Gsabg+D1R--GsD1R">
        <Reactant specieID="Gsabg"                      />
        <Reactant specieID="D1R"                      />
        <Product  specieID="GsD1R"                     />

        <forwardRate> 0.01e-03 </forwardRate>
        <reverseRate> 0.4e-03  </reverseRate>
    </Reaction>
    <!-- 2b. GsD1R + Da       < - > DaD1RGs       Kd=1000   source: Falkenburger J Gen Phys off-rate, Dreyer J Neurosci-->
    <Reaction name = "GsD1R+Da--DaD1RGs" id="GD1R+Da--DaD1RGs">
        <Reactant specieID="GsD1R"                     />
        <Reactant specieID="Da"                      />
        <Product  specieID="DaD1RGs"                    />

        <forwardRate> 0.005e-03 </forwardRate>
        <reverseRate> 5e-03        </reverseRate>
    </Reaction>

    <!-- 3.  DaD1RGs <-> DaD1R + GsaGTP +Gbg-->
        <Reaction name = "DaD1RGs-DaD1R+GsaGTP+Gbg reac" id="DaD1RGs-DaD1R+GsaGTP+Gbg_id">
        <Reactant specieID="DaD1RGs"                    />
        <Product  specieID="DaD1R"                  />
        <Product  specieID="GsaGTP"                  />
        <Product  specieID="Gbg"                  />

        <forwardRate> 0.15e-03        </forwardRate>
        <reverseRate> 0.0           </reverseRate>
    </Reaction>

<!--*****************PKAc phosphorylation of DaD1R *******************************-->
    <!--4. PKAc + DaD1RGs -> PKAcDaD1RGs Km= 125nM-->
    <Reaction name = "DaD1RGs phosp1" id="phospDaD1RGs1">
        <Reactant specieID="PKAc"                   />
        <Reactant specieID="DaD1RGs"                  />
        <Product  specieID="PKAcDaD1RGs"              />

        <forwardRate> 0.006e-03    </forwardRate>
        <reverseRate> 0.6e-03    </reverseRate>
    </Reaction>
    <!--5. PKAcDaD1RGs -> PKAc + phosphoDaD1RGs -->
    <Reaction name = "DaD1RGs phosp2" id="phospDaD1RGs2">
        <Reactant specieID="PKAcDaD1RGs"              />
        <Product  specieID="pDaD1RGs"                 />
        <Product  specieID="PKAc"                   />

        <forwardRate> 0.0e-03    </forwardRate>
        <reverseRate> 0             </reverseRate>
    </Reaction>

    <!--6a. pDaD1RGs -> pD1RGs - Da dissociation 1 uM-->
    <Reaction name = "Da_dissoc" id="Da_dissoc">
        <Reactant specieID="pDaD1RGs"              />
        <Product  specieID="pGsD1R"               />
        <Product  specieID="Da"               />

        <forwardRate>  0.1    </forwardRate>
        <reverseRate>  0.1e-3            </reverseRate>
    </Reaction>

    <!--6b. pD1RGs -> D1RGs - fast dephos of unbound receptor -->
    <Reaction name = "Da_dissoc" id="Da_dissoc">
        <Reactant specieID="pGsD1R"              />
        <Product  specieID="GsD1R"               />

        <forwardRate>  0.02e-3    </forwardRate>
        <reverseRate>  0            </reverseRate>
    </Reaction>

    <!--6c. pDaD1RGs -> DaD1RGs -->
    <Reaction name = "dephosD1R" id="dphospD1R">
        <Reactant specieID="pDaD1RGs"              />
        <Product  specieID="Gsabg"               />
        <Product  specieID="D1R"               />
        <Product  specieID="Da"               />

        <forwardRate>  0.0002e-03    </forwardRate>
        <reverseRate>  0            </reverseRate>
    </Reaction>

<!--III. *********** Gq coupled receptor, from GQ RXN FILE *************-->
<!--0a. Glu or Glu Agonist is extruded -->
    <!--0a. Injected DaDbuf dissociates to Dbuf (external) and Da: DaDbuf -> Da + Dbuf  -->
    <Reaction name = "Glubuf--Glu+Gbuf" id="GluGbuf--Glu+Gbuf">
        <Reactant specieID="GluGbuf"                      />
        <Product  specieID="Gbuf"                      />
        <Product  specieID="Glu"                     />
        <forwardRate> 20e-03 </forwardRate>
        <reverseRate> 0      </reverseRate>
    </Reaction>
    
    <!--0b. GluOut    Glu <-> GluOut>  -->
  <Reaction name = "Glu--GluOut" id="Glu--GluOut">
  	<Reactant specieID="Glu"/>
	<Product specieID="GluOut"/>

  	<forwardRate>1.2e-3</forwardRate>
  	<reverseRate>0.06e-6</reverseRate>
  </Reaction>
  
  <!--0c. GluOut eliminated to prevent baseline shift: GluOut + Gbuf <-> Null -->
    <Reaction name = "GluOut-buf reac" id="Glu-buf_id">
        <Reactant specieID="GluOut"                      />
        <Reactant specieID="Gbuf"                      />

        <forwardRate> 1e-6      </forwardRate>
        <reverseRate> 0      </reverseRate>
    </Reaction>
    
   <!--0c. GluMgluR <==> Desensitized, needed for prolonged DHPG application -->
      <Reaction name = "Glu+MgluR--GluMgluRdesens" id="Glu+MgluR--GluMgluRdesens">
        <Reactant specieID="GluMgluR"              />
        <Product  specieID="GluMgluRdesens"         />

        <forwardRate> 0.0625e-03 </forwardRate>
        <reverseRate> 0.001e-03      </reverseRate>
    </Reaction>

   <!--1a. Glu or Glu agonist Dhpg: Glu + MgluR <==> GluMgluR
    1st set of rates is for Dhpg, 2nd set of rates for Glu  -->
      <Reaction name = "Glu+MgluR--GluMgluR" id="Glu+MgluR--GluMgluR">
        <Reactant specieID="Glu"              />
        <Reactant specieID="MgluR"              />
        <Product  specieID="GluMgluR"         />

        <forwardRate> 0.001e-03 </forwardRate>
        <!--reverseRate> 6.6e-03      </reverseRate-->
	<!-- uncomment below and comment above for Glu (opposite for Dhpg) -->
        <reverseRate> 0.5e-03      </reverseRate>
    </Reaction>

    <!--2a. Gqabg + GluMgluR    <-> GluMgluRGq    -->
    <Reaction name = "Gqabg+GluMgluR--GluMgluRGq" id="Gqabg+GluMgluR--GluMgluRGq">
        <Reactant specieID="Gqabg"               />
        <Reactant specieID="GluMgluR"             />
        <Product  specieID="GluMgluRGq"            />

        <forwardRate>  0.009e-03  </forwardRate>
        <reverseRate>   1.36e-03  </reverseRate>
    </Reaction>

  <!--1b. Gqabg + MgluR <-> MgluRGq -->
  <Reaction name = "Gqabg+MgluR- -MgluRGq" id="Gqabg+MgluR- -MgluRGq">
        <Reactant specieID="Gqabg" />
        <Reactant specieID="MgluR" />
        <Product specieID="MgluRGq" />

        <forwardRate> 0.00225e-06 </forwardRate>
        <reverseRate> 0.68e-03 </reverseRate>
   </Reaction>

   <!--2b. Glu + MgluRGq <-> GluMgluRGq -->
   <Reaction name = "Glu+MgluRGq- -GluMgluRGq" id="Glu+MgluRGq- -GluMgluRGq">
        <Reactant specieID="Glu" />
        <Reactant specieID="MgluRGq" />
        <Product specieID="GluMgluRGq" />

        <forwardRate> 0.004e-03 </forwardRate>
        <!--reverseRate> 13.2e-03      </reverseRate-->
	<!-- uncomment below and comment above for Glu (opposite for Dhpg) -->
        <reverseRate> 1e-03 </reverseRate>
   </Reaction>

   <!--3. GabgGluMglu    <-> GqaGTP + GluMgluRGbg -->
    <Reaction name = "GluMgluRGq--GqaGTP+GluMgluRGbg" id="GluMgluRGq--GqaGTP+GluMgluRGbg">
        <Reactant specieID="GluMgluRGq"               />
        <Product specieID="GqaGTP"             />
        <Product specieID="GluMgluR"            /> 
        <Product specieID="Gbg"             />
 
        <forwardRate>  1.5e-03 </forwardRate>
        <reverseRate>   0  </reverseRate>
    </Reaction>

    <!-- *********** Gq coupled m1 ACh receptor  ***************-->
   <!--1a. ACh binding to m1R: ACh + m1R <=> AChm1R  -->
      <Reaction name = "ACh+m1R--AChm1R" id="ACh+m1R--AChm1R">
        <Reactant specieID="ACh"              />
        <Reactant specieID="m1R"              />
        <Product  specieID="AChm1R"         />

        <forwardRate> 0.095e-06 </forwardRate>
        <reverseRate> 2.5e-03      </reverseRate>
    </Reaction>

    <!--2a. Gqabg + AChm1R    <-> AChm1RGq  - make lower than for mGluR, to decrease basal Gq  -->
    <Reaction name = "Gqabg+AChm1R--AChm1RGq" id="Gqabg+AChm1R--AChm1RGq">
        <Reactant specieID="Gqabg"               />
        <Reactant specieID="AChm1R"             />
        <Product  specieID="AChm1RGq"            />

        <forwardRate>  0.024e-03  </forwardRate>
        <reverseRate>  0.42e-03  </reverseRate>
    </Reaction>

  <!--1b. Gqabg + m1R <-> m1RGq -->
  <Reaction name = "Gqabg+m1R- -m1RGq" id="Gqabg+m1R- -m1RGq">
        <Reactant specieID="Gqabg" />
        <Reactant specieID="m1R" />
        <Product specieID="m1RGq" />

        <forwardRate> 0.000576e-03 </forwardRate>
        <reverseRate> 0.42e-03  </reverseRate>
   </Reaction>

   <!--2b. ACh + m1RGq <-> AChm1RGq: 20x higher affinity than Glu binding mGluR-->
   <Reaction name = "ACh+m1RGq- -AChm1RGq" id="ACh+m1RGq- -AChm1RGq">
        <Reactant specieID="ACh" />
        <Reactant specieID="m1RGq" />
        <Product specieID="AChm1RGq" />

        <forwardRate> 0.00396e-03 </forwardRate>
        <reverseRate> 2.5e-03        </reverseRate>
   </Reaction>

   <!--3. GabgAChMglu    <-> GqaGTP + AChm1RGbg -->
    <Reaction name = "AChm1RGq--GqaGTP+AChm1RGbg" id="AChm1RGq--GqaGTP+AChm1RGbg">
        <Reactant specieID="AChm1RGq"               />
        <Product specieID="GqaGTP"             />
        <Product specieID="AChm1R"            /> 
        <Product specieID="Gbg"             />
 
        <forwardRate>  0.5e-03 </forwardRate>
        <reverseRate>   0  </reverseRate>
    </Reaction>

    <!-- *********** Gi coupled m4 receptor  ***************-->
    <!--0. ACh        -> null      -->
    <Reaction name = "ACh--null" id="ACh--null">
        <Reactant specieID="ACh"                      />
 
        <forwardRate> 6e-03 </forwardRate>
    </Reaction>
   <!-- ACh or ACh agonist: ACh + m4R <==> AChm4R       Kd = 7.4uM: low affinity Leach 2010 -->
      <Reaction name = "ACh+m4R--AChm4R" id="ACh+m4R--AChm4R">
        <Reactant specieID="ACh"              />
        <Reactant specieID="m4R"              />
        <Product  specieID="AChm4R"         />

        <forwardRate> 0.000338e-03 </forwardRate>
        <reverseRate> 2.5e-03      </reverseRate>
    </Reaction>

   <!-- Giabg + AChm4R    <-> GiabgAChm4R    Kd = 17.5  source:  sengeles JBiolChem 265 -->
    <Reaction name = "Giabg+AChm4R--AChm4RGi" id="Giabg+AChm4R--AChm4RGi">
        <Reactant specieID="AChm4R"             />
        <Reactant specieID="Giabg"               />
        <Product  specieID="AChm4RGi"            />

        <forwardRate>  0.192e-03  </forwardRate>
        <reverseRate>  3.36e-03  </reverseRate>
    </Reaction>

    <!-- Gi + m4R       <-> Gim4R     Kd = 236  source:  PMR, Hein et al. JBC 2006: Gi dissoc tau=14s  -->
    <Reaction name = "Giabg+m4R--Gim4R" id="Giabg+m4R--Gim4R">
        <Reactant specieID="Giabg"                      />
        <Reactant specieID="m4R"                      />
        <Product  specieID="Gim4R"                     />

        <forwardRate> 0.00178e-03 </forwardRate>
        <reverseRate> 0.42e-03  </reverseRate>
    </Reaction>
    <!-- Gim4R + ACh    <-> AChm4RGi     Kd = 548 nM: high affinity (4x greater than measured)-->
    <Reaction name = "Gim4R+ACh--AChm4RGi" id="Gm4R+ACh--AChm4RGi">
        <Reactant specieID="Gim4R"                     />
        <Reactant specieID="ACh"                      />
        <Product  specieID="AChm4RGi"                    />

        <forwardRate> 0.0365e-03 </forwardRate>
        <reverseRate> 20.0e-03        </reverseRate>
    </Reaction>

   <!--    AChm4RGiabg   <-> GiaGTP + AChm4R +Gbg   -->
    <Reaction name = "AChm4RGi--GiaGTP+AChm4R+Gbg" id="AChm4RGi--GiaGTP+AChm4R+Gbg">
        <Reactant specieID="AChm4RGi"               />
        <Product specieID="GiaGTP"             />
        <Product  specieID="AChm4R"                     />
        <Product  specieID="Gbg"                    />

        <forwardRate>  8.0e-03 </forwardRate>
        <reverseRate>   0  </reverseRate>
    </Reaction>

<!--IV. *************** G protein hydrolysis and regeneration  *******************-->
    <!--1. hydrolysis: GsaGTP       <-> GsaGDP             -->
    <Reaction name = "GsaGTP--GsaGDP reac" id="GsaGTP--GsaGDP_id">
        <Reactant specieID="GsaGTP"                  />
        <Product  specieID="GsaGDP"                  />

        <forwardRate> 0.01e-03        </forwardRate>
        <reverseRate> 0.0           </reverseRate>
    </Reaction>

    <!-- slow this down if depletion is significant, or to match regen of Gqa -->
    <!--2. regen: GsaGDP + Gbg       <-> Gsabg          (in xpp: k5=100), Kd=? -->
    <Reaction name = "GsaGDP+Gbg--Gs reac" id="GsaGDP+Gbg--Gs_id">
        <Reactant specieID="GsaGDP"                  />
        <Reactant specieID="Gbg"                    />
        <Product  specieID="Gsabg"                      />

        <forwardRate> 2e-03       </forwardRate>
        <reverseRate> 0.0           </reverseRate>
    </Reaction>

<!-- Hydrolysis of GqaGTP - slower than with GAP activity -->
    <!--3. GqaGTP <-> GqaGDP -->
    <Reaction name = "GqaGTP--GqaGDP" id="GqaGTP--GqaGDP">
        <Reactant specieID="GqaGTP"            />
        <Product  specieID="GqaGDP"            />

        <forwardRate>   0.1e-03   </forwardRate>
        <reverseRate>   0  </reverseRate>
    </Reaction>

<!-- 2nd order (was 1st order in Gq files) regeneration of Gqabg -->
    <!--4. GqaGDP + Gbg <-> Gqabg -->
    <Reaction name = "GqaGDP+Gbg--Gqabg" id="GqaGDP+Gbg--Gqabg">
        <Reactant specieID="GqaGDP"            />
        <Reactant specieID="Gbg"                    />
        <Product  specieID="Gqabg"            />

        <forwardRate>   2e-03   </forwardRate>
        <reverseRate>   0  </reverseRate>
    </Reaction>

<!-- Hydrolysis of GiaGTP - slower than with GAP activity  source: sengeles JBiolChem 265 -->
    <Reaction name = "GiaGTP--GiaGDP" id="GiaGTP--GiaGDP">
        <Reactant specieID="GiaGTP"            />
        <Product  specieID="GiaGDP"            />

        <forwardRate>   4.0e-03   </forwardRate>
        <reverseRate>   0  </reverseRate>
    </Reaction>

<!-- 2nd order  regeneration of Giabg source: -->
    <Reaction name = "GiaGDP--Giabg" id="GiaGDP--Giabg">
        <Reactant specieID="GiaGDP"            />
        <Reactant specieID="Gbg"                    />
        <Product  specieID="Giabg"            />

        <forwardRate>   2e-03   </forwardRate>
        <reverseRate>   0  </reverseRate>
    </Reaction>

<!-- ***************************************************************************-->
<!--V. AC5 to cAMP with PDEs, from Gs RXN FILE. May need to add AC1 at some point -->
    <!--1. GsaGTP + AC5 <-> AC5Gsa(GTP) -->
    <Reaction name = "GsaGTP+AC5--AC5Gsa reac" id="GsaGTP+AC5--AC5Gsa_id">
        <Reactant specieID="GsaGTP"                  />
        <Reactant specieID="AC5"                     />
        <Product  specieID="AC5Gsa"                />

        <forwardRate> 0.0148e-03   </forwardRate>
        <reverseRate> 3.996e-03        </reverseRate>
    </Reaction>
    <!--2. AC5Gsa(GTP) + ATP    <-> AC5Gsa(GTP)ATP     -->
    <Reaction name = "AC5Gsa+ATP--AC5GsaATP reac" id="AC5Gsa+ATP--AC5GsaATP_id">
        <Reactant specieID="AC5Gsa"                />
        <!--Reactant specieID="ATP"                    /-->
        <Product  specieID="AC5GsaATP"             />

        <!--if ATP: forwardRate> 0.1276e-6    </forwardRate-->
        <forwardRate> 0.2552    </forwardRate>
        <reverseRate> 0.2612e-03    </reverseRate>
    </Reaction>
    <!--3. AC5Gsa(GTP)ATP       <-> AC5Gsa(GTP) + cAMP   -->
    <Reaction name = "AC5GsaATP--AC5Gsa+cAMP reac" id="AC5GsaATP--AC5Gsa+cAMP_id">
        <Reactant specieID="AC5GsaATP"             />
        <Product  specieID="AC5Gsa"                />
        <Product  specieID="cAMP"                   />

        <forwardRate> 28.46e-03     </forwardRate>
        <reverseRate> 0.2592e-6    </reverseRate>
    </Reaction>
    
    <Reaction name = "AC5GsaATP--AC5Gsa+cAMP reac" id="AC5GsaATP--AC5Gsa+cAMP_id">
        <Reactant specieID="AC5GsaATP"             />
        <Product  specieID="AC5"                />
        <Product  specieID="cAMP"                   />
        <Product  specieID="GsaGDP"                   />

        <forwardRate> 0.03e-03     </forwardRate>
        <reverseRate> 0.0    </reverseRate>
    </Reaction>
    
<!-- 2a) GiaGTP + AC5 <-> AC5GiaGTP  Kd=160 for AC5: Chen-Goodspeed JBC 280-1808, Nielson JBC 271-33308 1996 -->
    <Reaction name = "GiaGTP_AC5_reac" id="GiaGTP_AC5_reac">
	<Reactant specieID="GiaGTP"/>
	<Reactant specieID="AC5"/>
	<Product specieID="AC5Gia"/>

	<forwardRate>0.0125e-3</forwardRate>
	<reverseRate>2e-3</reverseRate>
    </Reaction>

<!-- 2a) GiaGTP + AC5Gsa <-> AC5GsaGTP-GiaGTP  Kd=160 for AC5: Chen-Goodspeed JBC 280-1808, Nielson JBC 271-33308 1996 -->
    <Reaction name = "GiaGTP_AC5GsaGTP_reac" id="GiaGTP_AC5GsaGTP_reac">
	<Reactant specieID="GiaGTP"/>
	<Reactant specieID="AC5Gsa"/>
	<Product specieID="AC5GsaGia"/>

	<forwardRate>0.0125e-3</forwardRate>
	<reverseRate>6e-3</reverseRate>
    </Reaction>
    <Reaction name = "GsaGTP_AC5GiaGTP_reac" id="GsaGTP_AC5GiaGTP_reac">
	<Reactant specieID="GsaGTP"/>
	<Reactant specieID="AC5Gia"/>
	<Product specieID="AC5GsaGia"/>

        <forwardRate> 0.0037e-03   </forwardRate>
	<reverseRate> 2.997e-03</reverseRate>
    </Reaction>
    <!-- AC5GsaGia + ATP    <-> AC5GsaGiaATP       source: Dessauer CW, Gilman AG JBC 1997-->
    <Reaction name = "AC5GsaGia+ATP--AC5GsaGiaATP" id="AC5GsaGia+ATP--AC5GsaGiaATP">
        <Reactant specieID="AC5GsaGia"                />
        <!--Reactant specieID="ATP"                    /-->
        <Product  specieID="AC5GsaGiaATP"             />

        <!-- if ATP:forwardRate> 0.01276e-6    </forwardRate-->
        <forwardRate> 0.02552    </forwardRate>
        <reverseRate> 0.02612e-03    </reverseRate>
    </Reaction>
    
    <!-- AC5GsaGTPGiaGTP_ATP       <-> AC5GsaGTPGiaGTP + CAMP   source:  Dessauer CW, Gilman AG JBC 1997-->
    <Reaction name = "AC5GsaGiaATP--AC5GsaGia+cAMP" id="AC5GsaGiaATP--AC5GsaGia+cAMP">
        <Reactant specieID="AC5GsaGiaATP"             />
        <Product  specieID="AC5GsaGia"                />
        <Product  specieID="cAMP"                   />

        <forwardRate> 0.2746e-03     </forwardRate>
        <reverseRate> 0.2592e-6    </reverseRate>
    </Reaction>
    <!-- Gap activity for part of AC5GsaGiaATP-->
    <Reaction name = "AC5GsaGiaATP--AC5Gia+Gs+cAMP" id="AC5GsaGiaATP--AC5Gia+Gs+cAMP">
        <Reactant specieID="AC5GsaGiaATP"             />
        <Product  specieID="AC5Gsa"                />
        <Product  specieID="cAMP"                   />
        <Product  specieID="GiaGDP"                   />

        <forwardRate> 0.4e-03     </forwardRate>
        <reverseRate> 0.0    </reverseRate>
    </Reaction>

<!-- Now, those involving AC5 with Ca attached: -->
    <!--0b. AC5 + Ca    <-> AC5Ca     (in xpp: k9=0.001 k_9=0.9), 900 nM -->
<!--    <Reaction name = "AC5Ca reac" id="AC5Caid">
        <Reactant specieID="AC5"                     />
        <Reactant specieID="Ca"                     />
        <Product  specieID="AC5Ca"                   />

        <forwardRate> 0.001e-03     </forwardRate>
        <reverseRate> 0.9e-03       </reverseRate>
    </Reaction>
-->   <!--1b. GsaGTP + AC5Ca  <-> AC5Gsa(GTP)Ca  (slowed down from xpp: k6_2=0.0192, k_6_2=25) -->
<!--    <Reaction name = "AC5GsaCa reac" id="AC5GsaCaid">
        <Reactant specieID="GsaGTP"                  />
        <Reactant specieID="AC5Ca"                   />
        <Product  specieID="AC5GsaCa"              />

        <forwardRate> 0.00037e-03 </forwardRate>
        <reverseRate> 0.1e-03        </reverseRate>
    </Reaction>
-->    <!--2b. AC5Gsa(GTP)Ca + ATP  <-> AC5Gsa(GTP)CaATP      -->
<!--        <Reaction name = "AC5GsaCaATP reac" id="AC5GsaCaATP1id">
        <Reactant specieID="AC5GsaCa"              />
        <Reactant specieID="ATP"                    />
        <Product  specieID="AC5GsaCaATP"           />

        <forwardRate> 0.0638e-06 </forwardRate>
        <reverseRate> 0.1306e-03    </reverseRate>
    </Reaction>
-->   <!--3b. AC5Gsa(GTP)CaATP  <-> cAMP + AC5Gsa(GTP)Ca  -->
<!--    <Reaction name = "AC5GsaCaATP<->cAMP+AC5GsaCa reac" id="AC5GsaCaATP2id">
        <Reactant specieID="AC5GsaCaATP"           />
       <Product  specieID="cAMP"                   />
        <Product  specieID="AC5GsaCa"              />

        <forwardRate> 14.23e-03     </forwardRate>
        <reverseRate> 0.1296e-06 </reverseRate>
    </Reaction>
-->
<!-- ############### AC1 activated by Gs and CamCa4 ###################-->
<!-- 1a) GsaGTP + AC1 <-> AC1GsaGTP   -->
    <Reaction name = "GsaGTP_AC1_reac" id="GsaGTP_AC1_reac">
	<Reactant specieID="GsaGTP"/>
	<Reactant specieID="AC1"/>
	<Product specieID="AC1Gsa"/>

	<forwardRate>0.0385e-3</forwardRate>
	<reverseRate>10e-3</reverseRate>
	<Q10>0.2</Q10>
    </Reaction>

<!-- 1b) AC1GsaGTP + CamCa4 <-> AC1GsaGTPCamCa4    -->
    <Reaction name = "AC1GsaGTP_CamCa4_Reac" id="AC1GsaGTP_CamCa4_Reac">
	<Reactant specieID="AC1Gsa"/>
	<Reactant specieID="CamCa4"/>
	<Product specieID="AC1GsaCamCa4"/>

	<forwardRate>0.006e-3</forwardRate>
	<reverseRate>0.9e-3</reverseRate>
	<Q10>0.2</Q10>
    </Reaction>

<!-- 1c) AC1GsaGTPCamCa4 + ATP <-> AC1GsaGTPCamCa4ATP    -->
    <Reaction name = "AC1GsaGTPCamCa4_ATP_Reac" id="AC1GsaGTPCamCa4_ATP_Reac">
	<Reactant specieID="AC1GsaCamCa4"/>
	<!--Reactant specieID="ATP"/-->
	<Product specieID="AC1GsaCamCa4ATP"/>

	<!-- if ATP: forwardRate>0.01e-3</forwardRate-->
	<forwardRate>20e-3</forwardRate>
	<reverseRate>2273e-3</reverseRate>
	<Q10>0.2</Q10>
    </Reaction>

<!-- 1d)AC1GsaGTPCamCa4ATP -> AC1GsaGTPCamCa4 + cAMP    -->
    <Reaction name = "AC1GsaGTPCamCa4ATP_diss" id="AC1GsaGTPCamCa4ATP_diss">
	<Reactant specieID="AC1GsaCamCa4ATP"/>
	<Product specieID="cAMP"/>
	<Product specieID="AC1GsaCamCa4"/>

	<forwardRate>56.84e-3</forwardRate>
	<reverseRate>0</reverseRate>
	<Q10>0.2</Q10>
    </Reaction>

<!-- 5a) AC1 + CamCa4 <-> AC1Cam    -->
    <Reaction name = "AC1CamCa4_Reac" id="AC1CamCa4_Reac">
	<Reactant specieID="AC1"/>
	<Reactant specieID="CamCa4"/>
	<Product specieID="AC1CamCa4"/>

	<forwardRate>0.006e-3</forwardRate>
	<reverseRate>0.9e-3</reverseRate>
	<Q10>0.2</Q10>
    </Reaction>

<!-- 5b) AC1Cam + ATP <-> AC1CamATP    -->
    <Reaction name = "AC1CamCa4ATP_bind" id="AC1CamCa4ATP_bind">
	<Reactant specieID="AC1CamCa4"/>
	<!--Reactant specieID="ATP"/-->
	<Product specieID="AC1CamCa4ATP"/>

	<!-- if ATP:forwardRate>0.01e-3</forwardRate-->
	<forwardRate>20</forwardRate>
	<reverseRate>2273e-3</reverseRate>
	<Q10>0.2</Q10>
    </Reaction>

<!-- 5c) AC1CamATP -> AC1Cam +cAMP    -->
    <Reaction name = "AC1CamCa4ATP_disso" id="AC1CamCa4ATP_disso">
	<Reactant specieID="AC1CamCa4ATP"/>
	<Product specieID="cAMP"/>
	<Product specieID="AC1CamCa4"/>

	<forwardRate>5.684e-3</forwardRate>
	<reverseRate>0</reverseRate>
	<Q10>0.2</Q10>
    </Reaction>
    
<!--VI. *****************PDE1 *******************************-->
    <!--1. PDE1 + CamCa4  <-> PDE1CamCa4           (in xpp: KfpdeCam=0.1, KbpdeCam=1) -->
    <Reaction name = "PDE1+CamCa4--PDE1CamCa4" id="PDE1+CamCa4--PDE1CamCa4_id">
        <Reactant specieID="PDE1"                   />
        <Reactant specieID="CamCa4"                 />
        <Product  specieID="PDE1CamCa4"             />

        <forwardRate> 0.01e-03       </forwardRate>
        <reverseRate> 0.1e-03       </reverseRate>
    </Reaction>
    <!-- PDE1CamCa4 + cAMP <-> PDE1CamCa4cAMP         (in xpp: KfPde1=0.0046 KbPde1=44) -->
    <Reaction name = "PDE1CamCa4+cAMP--PDE1CamCa4cAMP" id="PDE1CamCa4+cAMP--PDE1CamCa4cAMP_id">
        <Reactant specieID="PDE1CamCa4"             />
        <Reactant specieID="cAMP"                   />
        <Product  specieID="PDE1CamCa4cAMP"               />

        <forwardRate> 0.0046e-03    </forwardRate>
        <reverseRate> 44.0e-03      </reverseRate>
    </Reaction>
    <!-- PDE1CamCa4cAMP        -> PDE1CamCa4 + AMP    (in xpp: V_Pde1=11) -->
    <Reaction name = "PDE1CamCa4cAMP--PDE1CamCa4+AMP" id="PDE1CamCa4cAMP--PDE1CamCa4+AMP_id">
        <Reactant specieID="PDE1CamCa4cAMP"               />
        <Product  specieID="PDE1CamCa4"             />
        <Product  specieID="AMP"                    />

        <forwardRate> 11.00e-03     </forwardRate>
        <reverseRate> 0.0           </reverseRate>
    </Reaction>

<!--VII. *****************PDE10 *******************************-->
    <!--1. PDE10 + cAMP    <-> PDE10cAMP         (in xpp: KfPDE10=    KbPDE10=  ) -->
    <Reaction name = "PDE10+cAMP--PDE10cAMP" id="PDE10+cAMP--PDE10cAMP_id">
        <Reactant specieID="PDE10"                  />
        <Reactant specieID="cAMP"                   />
        <Product  specieID="PDE10cAMP"              />

        <forwardRate> 0.084e-3        </forwardRate>
        <reverseRate> 16.8e-3        </reverseRate>
    </Reaction>
    <!--2. PDE10cAMP        -> PDE10 + AMP       (in xpp: V_PDE10=18) -->
    <Reaction name = "PDE10cAMP--PDE10+AMP" id="PDE10cAMP--PDE10+AMP_id">
        <Reactant specieID="PDE10cAMP"              />
        <Product  specieID="PDE10"                  />
        <Product  specieID="AMP"                    />

        <forwardRate> 4.2e-3         </forwardRate>
        <reverseRate> 0.0           </reverseRate>
    </Reaction>

<!--IX. *****************pPDE10 activity *******************************-->
    <!--1. pPDE10 + cAMP    <-> pPDE10cAMP          -->
    <Reaction name = "pPDE10+cAMP--pPDE10cAMP" id="pPDE10+cAMP--pPDE10cAMP_id">
        <Reactant specieID="pPDE10"                 />
        <Reactant specieID="cAMP"                   />
        <Product  specieID="pPDE10cAMP"             />

        <forwardRate>  0.336e-3      </forwardRate>
        <reverseRate>  67.2e-3        </reverseRate>
    </Reaction>

    <!--2. pPDE10cAMP        -> pPDE10 + AMP       source: -->
    <Reaction name = "pPDE10cAMP--pPDE10+AMP" id="pPDE10cAMP--pPDE10+AMP_id">
        <Reactant specieID="pPDE10cAMP"             />
        <Product  specieID="pPDE10"                 />
        <Product  specieID="AMP"                    />

        <forwardRate>  16.8e-3        </forwardRate>
        <reverseRate>  0.0          </reverseRate>
    </Reaction>

    <!--3. AMP             -> ATP              (in xpp: katp=10) -->
    <Reaction name = "AMP-ATP" id="AMP-AMP"> 
        <Reactant specieID="AMP"                    />
        <!--Product specieID="ATP"                    /-->
	<!-- eliminate product if no ATP -->
        <forwardRate> 0.1e-03      </forwardRate>
        <reverseRate> 0.0           </reverseRate>
    </Reaction>

<!-- *****************PDE4 and pPDE4 activity *******************************-->
    <!-- 15)  cAMP + PDE4  <-> PDE4cAMP -->
    <Reaction name = "PDE4 enzyme1" id="PDE4bind">
        <Reactant specieID="PDE4"           />
        <Reactant specieID="cAMP"            />
        <Product  specieID="PDE4cAMP"       />
        <forwardRate> 0.0216e-03  </forwardRate>
        <reverseRate> 68.95e-03    </reverseRate>
    </Reaction>

    <!-- 16)  PDE4cAMP -> AMP + PDE4 -->
    <Reaction name = "PDE4 actvcomp" id="PDE4cat">
        <Reactant specieID="PDE4cAMP"       />
        <Product  specieID="PDE4"           />
        <Product  specieID="AMP"             />
        <forwardRate> 17.233e-03    </forwardRate>
        <reverseRate> 0            </reverseRate>
    </Reaction>

    <!-- 17)  cAMP + pPDE4  <-> pPDE4cAMP -->
    <Reaction name = "pPDE4 enzyme1" id="pPDE4bind">
        <Reactant specieID="pPDE4"           />
        <Reactant specieID="cAMP"             />
        <Product  specieID="pPDE4cAMP"       />
        <forwardRate> 0.0864e-03   </forwardRate>
        <reverseRate> 275.8e-3  </reverseRate>
    </Reaction>

    <!-- 18)  pPDE4cAMP -> AMP + pPDE4 -->
    <Reaction name = "pPDE4 actvcomp" id="pPDE4cat">
        <Reactant specieID="pPDE4cAMP"       />
        <Product  specieID="pPDE4"           />
        <Product  specieID="AMP"              />
        <forwardRate> 68.932e-3   </forwardRate>
        <reverseRate> 0            </reverseRate>
    </Reaction>

<!-- extra PDE, called PDE2, requires 2 cAMP binding for activity -->
<!-- PDE2 + cAMP    <-> PDE2cAMP       Km=40 uM, source: WadaJBiolChem262-5139
Not allowing this single bound form to be active -->
    <Reaction name = "PDE2+cAMP--PDE2cAMP" id="PDE2+cAMP--PDE2cAMP">
        <Reactant specieID="PDE2"                  />
        <Reactant specieID="cAMP"                   />
        <Product  specieID="PDE2cAMP"              />

        <forwardRate> 0.00002e-3        </forwardRate>
        <reverseRate> 0.5e-3        </reverseRate>
    </Reaction>
    <!-- PDE2cGMP+cAMP        <-> PDE2cGMPcAMP -> PDE2cGMP + AMP   kD=1.0 uM, Kc
at=18x source: WadaJBiolChem262-5139   -->
    <Reaction name = "PDE2cAMP+cAMP--PDE2cAMP2" id="PDE2cAMP+cAMP--PDE2cAMP2">
        <Reactant specieID="PDE2cAMP"              />
        <Reactant specieID="cAMP"                   />
	<Product specieID="PDE2cAMP2"              />
        <forwardRate> 0.0059e-3         </forwardRate>
        <reverseRate> 0.5e-3           </reverseRate>
    </Reaction>
  
    <Reaction name = "PDE2cAMP2--PDE2cAMP+AMP" id="PDE2cAMP2--PDE2cAMP+AMP">
	<Reactant specieID="PDE2cAMP2"              />
        <Product specieID="PDE2cAMP"              />
        <Product  specieID="AMP"                    />
        <forwardRate> 5.4e-3         </forwardRate>
        <reverseRate> 0.0           </reverseRate>
    </Reaction>

    <!--VIII. *****************PKAc phosphorylation of PDE10 and PP2A dephos*************-->
<!-- slower than previous,  based on A. Chay and cAMP decay. Km=120nM-->
    <!--1a. PKAc + PDE10 -> PKAcPDE10 -->
    <Reaction name = "PDE10 phosp1" id="phospPDE101">
        <Reactant specieID="PKAc"                   />
        <Reactant specieID="PDE10"                  />
        <Product  specieID="PKAcPDE10"              />

        <forwardRate> 0.25e-06    </forwardRate>
        <reverseRate> 0.024e-03    </reverseRate>
    </Reaction>

    <!--2a. PKAcPDE10 -> PKAc + pPDE10 -->
    <Reaction name = "PDE10 phosp2" id="phospPDE102">
        <Reactant specieID="PKAcPDE10"              />
        <Product  specieID="pPDE10"                 />
        <Product  specieID="PKAc"                   />

        <forwardRate> 0.00e-03    </forwardRate>
        <reverseRate> 0             </reverseRate>
    </Reaction>

   <!--1b. PKAc + PDE10cAMP -> PKAcPDE10cAMP -->
    <Reaction name = "PDE10cAMP phosp1" id="phospPDE10cAMP1">
        <Reactant specieID="PKAc"                  />
        <Reactant specieID="PDE10cAMP"             />
        <Product  specieID="PKAcPDE10cAMP"         />

        <forwardRate> 0.25e-06    </forwardRate>
        <reverseRate> 0.024e-03    </reverseRate>
    </Reaction>

    <!--2b. PKAcPDE10cAMP -> PKAc + pPDE10cAMP -->
    <Reaction name = "PDE10cAMP phosp2" id="phospPDE10cAMP2">
        <Reactant specieID="PKAcPDE10cAMP"         />
        <Product  specieID="pPDE10cAMP"            />
        <Product  specieID="PKAc"                  />

        <forwardRate> 0.00e-03    </forwardRate>
        <reverseRate> 0             </reverseRate>
    </Reaction>

    <!-- 23,24)  pPDE10 +PP2ABPR72 -> PDE10 -->
    <Reaction name = "PDE10 d_phosp1" id="dphospPDE10a">
        <Reactant specieID="pPDE10"          />
        <Reactant specieID="PP2ABPR72"          />
        <Product  specieID="pPDE10PP2A"           />
        <forwardRate> 0.024e-06     </forwardRate>
        <reverseRate> 0.0096e-3            </reverseRate>
    </Reaction>

    <Reaction name = "PDE10 d_phosp2" id="dphospPDE10b">
        <Reactant specieID="pPDE10PP2A"           />
        <Product specieID="PDE10"          />
        <Product specieID="PP2ABPR72"          />
        <forwardRate> 0.0024e-03     </forwardRate>
        <reverseRate> 0            </reverseRate>
    </Reaction>

    <!-- 25,26)  pPDE10 +PP2Acal -> PDE10 -->
    <Reaction name = "PDE10 d_phosp1" id="dphospPDE10a">
        <Reactant specieID="pPDE10"          />
        <Reactant specieID="PP2Acal"          />
        <Product  specieID="pPDE10PP2Ac"           />
        <forwardRate> 0.048e-06     </forwardRate>
        <reverseRate> 0.0192e-3            </reverseRate>
    </Reaction>

    <Reaction name = "PDE10 d_phosp2" id="dphospPDE10b">
        <Reactant specieID="pPDE10PP2Ac"           />
        <Product specieID="PDE10"          />
        <Product specieID="PP2Acal"          />
        <forwardRate> 0.0048e-03     </forwardRate>
        <reverseRate> 0            </reverseRate>
    </Reaction>

   <!-- 19)  PKAc + PDE4 -> PKAcPDE4 -->
    <Reaction name = "PDE4 phosp1" id="phospPDE41">
        <Reactant specieID="PKAc"            />
        <Reactant specieID="PDE4"           />
        <Product  specieID="PKAcPDE4"       />
        <forwardRate> 0.25e-6  </forwardRate>
        <reverseRate> 0.08e-3    </reverseRate>
    </Reaction>

    <!-- 20)  PKAcPDE4 -> PKAc + pPDE4 -->
    <Reaction name = "PDE4 phosp2" id="phospPDE42">
        <Reactant specieID="PKAcPDE4"       />
        <Product  specieID="pPDE4"          />
        <Product  specieID="PKAc"            />
        <forwardRate> 0.0e-3    </forwardRate>
        <reverseRate> 0            </reverseRate>
    </Reaction>

   <!-- 21)  PKAc + PDE4cAMP -> PKAcPDE4cAMP -->
    <Reaction name = "PDE4cAMP phosp1" id="phospPDE41cAMP">
        <Reactant specieID="PKAc"            />
        <Reactant specieID="PDE4cAMP"           />
        <Product  specieID="PKAcPDE4cAMP"       />
        <forwardRate> 0.25e-6  </forwardRate>
        <reverseRate> 0.08e-3    </reverseRate>
    </Reaction>

    <!-- 22)  PKAcPDE4cAMP -> PKAc + pPDE4cAMP -->
    <Reaction name = "PDE4cAMP phosp2" id="phospPDE42cAMP">
        <Reactant specieID="PKAcPDE4cAMP"       />
        <Product  specieID="pPDE4cAMP"          />
        <Product  specieID="PKAc"            />
        <forwardRate> 0.0e-3    </forwardRate>
        <reverseRate> 0            </reverseRate>
    </Reaction>

    <!-- 23,24)  pPDE4 +PP2ABPR72 -> PDE4 
    Resjo Biochem J 1999, Mol Pharmacol. 2008 De Arcangelis-->
    <Reaction name = "PDE4 d_phosp1" id="dphospPDE4a">
        <Reactant specieID="pPDE4"          />
        <Reactant specieID="PP2ABPR72"          />
        <Product  specieID="pPDE4PP2A"           />
        <forwardRate> 0.024e-06     </forwardRate>
        <reverseRate> 0.0096e-3            </reverseRate>
    </Reaction>

    <Reaction name = "PDE4 d_phosp2" id="dphospPDE4b">
        <Reactant specieID="pPDE4PP2A"           />
        <Product specieID="PDE4"          />
        <Product specieID="PP2ABPR72"          />
        <forwardRate> 0.0024e-03     </forwardRate>
        <reverseRate> 0            </reverseRate>
    </Reaction>

    <!-- 25,26)  pPDE4 +PP2Acal -> PDE4
    Resjo Biochem J 1999, Mol Pharmacol. 2008 De Arcangelis-->
    <Reaction name = "PDE4 d_phosp1" id="dphospPDE4a">
        <Reactant specieID="pPDE4"          />
        <Reactant specieID="PP2Acal"          />
        <Product  specieID="pPDE4PP2Ac"           />
        <forwardRate> 0.048e-06     </forwardRate>
        <reverseRate> 0.0192e-3            </reverseRate>
    </Reaction>

    <Reaction name = "PDE4 d_phosp2" id="dphospPDE4b">
        <Reactant specieID="pPDE4PP2Ac"           />
        <Product specieID="PDE4"          />
        <Product specieID="PP2Acal"          />
        <forwardRate> 0.0048e-03     </forwardRate>
        <reverseRate> 0            </reverseRate>
    </Reaction>

<!--X. **************************************************************************-->
<!-- PLC, Dag, IP3, 2ag and PKC, from Gq RXN FILE --> 
<!-- Review these and check all molecule names -->

    <!--1a. Plc+Ca <-> PlcCa 2500 nM -->
    <Reaction name = "Plc+Ca--PlcCa" id="Plc+Ca--PlcCa">
        <Reactant specieID="Ca"           />
        <Reactant specieID="Plc"              />
        <Product  specieID="PlcCa"               />

        <forwardRate> 0.0004e-03   </forwardRate>
        <reverseRate> 1e-03        </reverseRate>
    </Reaction>

    <!--2a. PlcCa + GaGTP    <->   PlcCaGqa  200 nM-->
    <Reaction name = "PlcCa+GqaGTP--PlcCaGqa" id="PlcCa+GqaGTP--PlcCaGqa">
        <Reactant specieID="GqaGTP"           />
        <Reactant specieID="PlcCa"              />
        <Product  specieID="PlcCaGqa"               />

        <forwardRate> 0.004375e-03   </forwardRate>
        <reverseRate> 0.7e-03        </reverseRate>
    </Reaction>

    <!--1b. Plc + GqaGTP    <->   PlcGqa 1000 nM -->
<!--AB: Falkenburger 2010 uses 0.71e-3 for reverse rate --> 
    <Reaction name = "Plc+GqaGTP--PlcGqa" id="Plc+GqaGTP--PlcGqa">
        <Reactant specieID="GqaGTP"           />
        <Reactant specieID="Plc"              />
        <Product  specieID="PlcGqa"               />

        <forwardRate> 0.0007e-03   </forwardRate>
        <reverseRate> 0.7e-03        </reverseRate>
    </Reaction>

    <!--2b. PlcGqa + Ca    <->   PlcCaGqa  500 nM-->
    <Reaction name = "PlcGaGTP+Ca--PlcCaGqa" id="PlcGaGTP+Ca--PlcCaGqa">
        <Reactant specieID="Ca"           />
        <Reactant specieID="PlcGqa"              />
        <Product  specieID="PlcCaGqa"               />

        <forwardRate> 0.0025e-03   </forwardRate>
        <reverseRate> 1.0e-03        </reverseRate>
    </Reaction>


   <!--3i. PlcCa + Pip2    <-> PlcCaPip2    Possibly make these two 3x-5x faster-->
    <Reaction name = "PlcCa+Pip2--PlcCaPip2" id="PlcCa+Pip2--PlcCaPip2">
        <Reactant specieID="PlcCa"               />
        <Reactant specieID="Pip2"             />
        <Product  specieID="PlcCaPip2"            />

        <forwardRate> 0.03e-06   </forwardRate>
        <reverseRate> 1.2e-03   </reverseRate>
    </Reaction>

    <!--4i. PlcCaPip2      <-> PlcCaDag + Ip3 -->
    <Reaction name = "PlcCaPip2--PlcCa+Dag+Ip3" id="PlcCaPip2--PlcCa+Dag+Ip3">
        <Reactant specieID="PlcCaPip2"            />
        <Product  specieID="PlcCa"               />
        <Product  specieID="Ip3"            />
        <Product  specieID="Dag"            />

        <forwardRate> 0.3e-03     </forwardRate>
        <reverseRate> 0e-03    </reverseRate>
    </Reaction>
      
    <!--3j. PlcCaGqa + Pip2    <-> PlcCaGqaPip2   Possibly make these two 3x-5x faster -->
    <Reaction name = "PlcCaGqa+Pip2--PlcCaGqaPip2" id="PlcCaGqa+Pip2--PlcCaGqaPip2">
        <Reactant specieID="PlcCaGqa"               />
        <Reactant specieID="Pip2"             />
        <Product  specieID="PlcCaGqaPip2"            />

        <forwardRate>  1.665e-06   </forwardRate>
        <reverseRate>  60e-03   </reverseRate>
    </Reaction>
      
    <!--4j. PlcCaGqaPip2       <-> PlcCaGqaDag + Ip3 -->
    <Reaction name = "PlcCaGqaPip2--PlcCaGqaDag+Ip3" id="PlcCaGqaPip2--PlcCaGqaDag+Ip3">
        <Reactant specieID="PlcCaGqaPip2"            />
        <Product  specieID="PlcCaGqa"               />
        <Product  specieID="Dag"            />
        <Product  specieID="Ip3"            />

        <forwardRate> 30e-03     </forwardRate>
        <reverseRate> 0e-03    </reverseRate>
    </Reaction>
      
<!-- GAP activity - only with PLC bound not to PIP2. Make slower for stronge 2AG response?-->
    <!-- PlcGaGTP       <-> Plc + Gabg -->
    <Reaction name = "PlcGqa--Plc+GqaGDP" id="PlcGqa--Plc+GqaGDP">
        <Reactant specieID="PlcGqa"            />
        <Product  specieID="Plc"               />
        <Product  specieID="GqaGDP"            />

        <forwardRate>   12e-03   </forwardRate>
        <reverseRate>   0  </reverseRate>
    </Reaction>

<!-- Gap activity of PlcCa.  Make slower for stronge 2AG response?-->
    <Reaction name = "PlcCaGqa--PlcCa+GaGDP" id="PlcCaGqa--Plc+GaGDP">
        <Reactant specieID="PlcCaGqa"            />
        <Product  specieID="PlcCa"               />
        <Product  specieID="GqaGDP"            />

        <forwardRate>   12e-03   </forwardRate>
        <reverseRate>   0  </reverseRate>
    </Reaction>

    <!-- Ca + Dgl <-> CaDgl   Dgl is DAG lipase, which produces 2AG -->
    <!-- no source for rates.  Make 400 nM affinity -->
    <Reaction name = "Ca+Dlg--CaDgl" id="Ca+Dlg--CaDgl">
        <Reactant specieID="Ca"            />
        <Reactant specieID="Dgl"               />
        <Product  specieID="CaDgl"            />

        <forwardRate> 0.125e-03     </forwardRate>
        <reverseRate> 50e-03    </reverseRate>
    </Reaction>
 
    <!-- Dag + CaDgl <-> DagCaDgl -->
    <!--affinity dec to 2500 nM   -->
    <Reaction name = "Dag+CaDlg--DagCaDgl" id="Dag+CaDlg--DagCaDgl">
        <Reactant specieID="Dag"            />
        <Reactant specieID="CaDgl"               />
        <Product  specieID="DagCaDgl"            />

        <forwardRate> 0.0005e-03     </forwardRate>
        <reverseRate> 1.0e-03    </reverseRate>
    </Reaction>

    <!-- DagCaDgl <-> CaDgl + 2ag -->
    <!-- kcat from Rosenburger Lipids 2007 -->
    <Reaction name = "DagCaDgl--CaDgl+2ag" id="DagCaDgl--CaDgl+2ag">
        <Reactant specieID="DagCaDgl"            />
        <Product  specieID="CaDgl"               />
        <Product  specieID="2ag"            />

        <forwardRate> 0.25e-03     </forwardRate>
        <reverseRate> 0e-03    </reverseRate>
    </Reaction>

<!-- ************* degradation of IP3 and 2AG, implementing the enzymes? -->
    <!--  Ip3    <-> Ip3degrad         rate from IP3deg from Xu watras Loew J Cell science 2003 -->
    <Reaction name = "Ip3--Ip3degrad" id="Ip3--Ip3degrad">
         <Reactant specieID="Ip3"            />
        <Product  specieID="Ip3degrad"        />

        <forwardRate> 0.1e-03      </forwardRate>
        <reverseRate> 0.0e-03      </reverseRate>
    </Reaction>

   <!-- previously unlabeled IP3 degradation rxn -->
   <Reaction name = "Ip3degrad+PIkinase--Ip3degPIk" id="PIkinase1">
        <Reactant specieID="Ip3degrad"            />   
        <Reactant  specieID="PIkinase"               />
        <Product  specieID="Ip3degPIk"            />

        <forwardRate> 0.0005e-3    </forwardRate>
        <reverseRate> 0.4e-03    </reverseRate>
    </Reaction>

<!-- rate from PIP2synth from Xu watras Loew J Cell science 2003 -->
   <Reaction name = "Ip3degPIk--PIP2 + PIkinase" id="PIkinase2">
        <Reactant specieID="Ip3degPIk"            />
        <Product  specieID="PIkinase"               />
        <Product  specieID="Pip2"            />

        <forwardRate> 0.1e-3  </forwardRate>
        <reverseRate> 0e-3    </reverseRate>
    </Reaction>    

    <!--  2ag    <-> 2agDegrad       Degraded 2AG   -->
    <Reaction name = "2ag--2agDegrad" id="2ag--2agDegrad">
         <Reactant specieID="2ag"            />
        <Product  specieID="2agDegrad"        />

        <forwardRate> 0.25e-03      </forwardRate>
        <reverseRate> 0.0e-03      </reverseRate>
    </Reaction>

	<!-- ************* degradation of  DAG by DAG kinase -->
     <!--  Dag   + DagK <-> DagKdag -> PA  step 1  (Km = 2 mol% Shulga et al. FEBS letters -->
    <Reaction name = "DagKdag1" id="DagKdag1">
         <Reactant specieID="Dag"            />
         <Reactant specieID="DagK"            />
        <Product  specieID="DagKdag"        />

        <forwardRate> 0.00007e-03      </forwardRate>
        <reverseRate> 0.8e-3         </reverseRate>
    </Reaction>

    <!--  Dag   + DagK <-> DagKdag -> PA   step 2 -->
    <Reaction name = "DagKdag1" id="DagKdag1">
         <Reactant specieID="DagKdag"            />
        <Product  specieID="PA"        />
        <Product  specieID="DagK"        />

        <forwardRate> 0.2e-03      </forwardRate>
        <reverseRate> 0.0e-03      </reverseRate>
    </Reaction>


<!-- These are values from Hellgren Kotaleski PKC paper. 2.5 uM affinity -->
    <!-- Pkc + Ca    <->   PkcCa  -->
    <Reaction name = "Pkc+Ca--PkcCa" id="Pkc+Ca--PkcCa">
        <Reactant specieID="Ca"           />
        <Reactant specieID="Pkc"              />
        <Product  specieID="PkcCa"               />

        <forwardRate> 0.020e-03   </forwardRate>
        <reverseRate> 50e-03        </reverseRate>
    </Reaction>
 
<!-- THese are values from Hellgren Kotaleski PKC paper. 10 uM affinity
MUCH slower binding compared to CaDgl  -->
   <!-- PkcCa + Dag    <-> PkcCaDag    -->
    <Reaction name = "PkcCa+Dag--PkcCaDag" id="PkcCa+Dag--PkcCaDag">
        <Reactant specieID="PkcCa"               />
        <Reactant specieID="Dag"             />
        <Product  specieID="PkcCaDag"            />

        <forwardRate> 0.015e-06   </forwardRate>
        <reverseRate>  0.15e-03   </reverseRate>
    </Reaction>

<!-- ***************************************************************************-->
<!--XI. PP2B, PP2A, PKA, Darpp32, CaMKII from Gs RXN FILE -->
<!-- ******* PKA from Asia Hippo Model ********* -->     
    <!--1) PKA + 2cAMP <-> PKAcAMP2 -->
    <Reaction name = "PKA_bind" id="PKA_bind">
	<Reactant specieID="PKA"/>
        <Reactant specieID="cAMP" n="2"/>
	<Product specieID="PKAcAMP2"/>


        <forwardRate>0.261e-06</forwardRate>
	<reverseRate>0.060e-03</reverseRate>
    </Reaction>

    <!--2) PKAcAMP2 + 2cAMP <-> PKAcAMP4 -->
    <Reaction name = "PKAcAMP2_bind" id="PKAcAMP2_bind">
	<Reactant specieID="PKAcAMP2"/>
        <Reactant specieID="cAMP" n="2"/>
	<Product specieID="PKAcAMP4"/>

	<forwardRate>0.35e-06</forwardRate>
	<reverseRate>0.6e-3</reverseRate>
    </Reaction>

<!--3) PKAcAMP4 <-> 2PKAr(as dimer) + 2PKAc(monomers) -->
    <Reaction name = "PKAcAMP4_diss" id="PKAcAMP4_diss">
	<Reactant specieID="PKAcAMP4"/>
	<Product specieID="PKAr"/>
	<Product specieID="PKAc" n="2"/>  

	<forwardRate>0.24e-03</forwardRate>
	<reverseRate>0.0255e-03</reverseRate>
    </Reaction>

    <!--1) Epac1-camps + cAMP <-> Epac1-camps_cAMP -->
    <Reaction name = "Epac_bind" id="Epac_bind">
	<Reactant specieID="Epac1"/>
        <Reactant specieID="cAMP"/>
	<Product specieID="Epac1cAMP"/>

        <forwardRate>0.033e-6</forwardRate>
	<reverseRate>0.08e-3</reverseRate>
	<Q10>0.2</Q10>
    </Reaction>

    <!-- Cam or CamC2N or CamC2C or CamCa4 binding to PP2B.  Check rates for microscopic reversibility -->
     <!--4x) Cam    +   PP2B     <->  PP2BCam     (in xpp: k33a=1 k_33a=3)  -->
    <Reaction name = "Cam+PP2B--PP2BCam reac" id="Cam+PP2B--PP2BCam_id">
        <Reactant specieID="Cam"                    />
        <Reactant specieID="PP2B"                   />
        <Product  specieID="PP2BCam"                />

        <forwardRate> 0.0046e-3       </forwardRate>
        <reverseRate> 0.0012e-3      </reverseRate>
    </Reaction>

    <!--4C) CamCa2C    +   PP2B     <->  PP2BCamCa2C (in xpp: k33c=1 k_33c=0.3) -->
    <Reaction name = "CamCa2C+PP2B--PP2BCamCa2C reac" id="CamCa2C+PP2B--PP2BCamCa2C_id">
        <Reactant specieID="CamCa2C"                 />
        <Reactant specieID="PP2B"                   />
        <Product  specieID="PP2BCamCa2C"             />

        <forwardRate> 0.046e-3       </forwardRate>
        <reverseRate> 0.0012e-3      </reverseRate>
    </Reaction>

    <!--4N) CamCa2N    +   PP2B     <->  PP2BCamCa2N (in xpp: k33c=1 k_33c=0.3) -->
    <Reaction name = "CamCa2N+PP2B--PP2BCamCa2N reac" id="CamCa2N+PP2B--PP2BCamCa2N_id">
        <Reactant specieID="CamCa2N"                 />
        <Reactant specieID="PP2B"                   />
        <Product  specieID="PP2BCamCa2N"             />

        <forwardRate> 0.046e-3       </forwardRate>
        <reverseRate> 0.0012e-3      </reverseRate>
    </Reaction>

    <!--5xC) PP2BCam    +   Ca2      <->  PP2BCamCa2C -->
    <Reaction name = "PP2BCam+Ca2--PP2BCamCa2C reac" id="PP2BCam+Ca2--PP2BCamCa2C_id">
        <Reactant specieID="PP2BCam"                />
        <Reactant specieID="Ca"        n="2"        />
        <Product  specieID="PP2BCamCa2C"             />

        <forwardRate> 6.0e-06       </forwardRate>
        <reverseRate> 0.91e-03      </reverseRate>
    </Reaction>

    <!--5xN) PP2BCam    +   Ca2      <->  PP2BCamCa2N -->
    <Reaction name = "PP2BCam+Ca2--PP2BCamCa2N reac" id="PP2BCam+Ca2--PP2BCamCa2N_id">
        <Reactant specieID="PP2BCam"                />
        <Reactant specieID="Ca"        n="2"        />
        <Product  specieID="PP2BCamCa2N"             />

        <forwardRate> 0.1e-03       </forwardRate>
        <reverseRate> 100e-03      </reverseRate>
    </Reaction>

    <!--7x) CamCa4    +  PP2B     <->  PP2BCamCa4 -->
    <Reaction name = "CamCa4+PP2B--PP2BCamCa4 reac" id="CamCa4+PP2B--PP2BCamCa4_id">
        <Reactant specieID="CamCa4"                 />
        <Reactant specieID="PP2B"                   />
        <Product  specieID="PP2BCamCa4"             />

        <forwardRate> 0.046e-3       </forwardRate>
        <reverseRate> 0.0012e-3      </reverseRate>
    </Reaction>

  <!-- PP2BCamCa2 +  Ca2     <->  PP2BCamCa4, either N site or C site -->
    <!--4N) N site binding -->
    <Reaction name = "PP2BCamCa2C+Ca2--PP2BCamCa4 reac" id="PP2BCamCa2+Ca2--PP2BCamCa4_id">
        <Reactant specieID="PP2BCamCa2C"             />
        <Reactant specieID="Ca"        n="2"        />
        <Product  specieID="PP2BCamCa4"             />

        <forwardRate> 0.1e-03       </forwardRate>
        <reverseRate> 1000e-03      </reverseRate>
    </Reaction>

    <!--4C) C site binding -->
    <Reaction name = "PP2BCamCa2N+Ca2--PP2BCamCa4 reac" id="PP2BCamCa2N+Ca2--PP2BCamCa4_id">
        <Reactant specieID="PP2BCamCa2N"             />
        <Reactant specieID="Ca"        n="2"        />
        <Product  specieID="PP2BCamCa4"             />

        <forwardRate> 6.0e-06       </forwardRate>
        <reverseRate> 9.1e-03      </reverseRate>
    </Reaction>

   <!--PKAc + PP2AB56d    <->  PKAcPP2AB56d    Km=172nM  (in xpp: k27=0.0025 k_27=0.3) -->
    <Reaction name = "PKAc+PP2A--PKAcPP2AB56d reac" id="PKAc+PP2A--PKAcPP2AB56d_id">
        <Reactant specieID="PP2AB56d"          />
        <Reactant specieID="PKAc"               />
        <Product  specieID="PKAcPP2AB56d"      />

        <forwardRate> 0.00125e-03      </forwardRate>
        <reverseRate> 0.185e-03         </reverseRate>
    </Reaction>

    <!--PKAcPP2AB56d        ->  PKAc + pPP2A(_B56d)   (in xpp: v27=0.1) -->
    <Reaction name = "PKAcPP2AB56d--PKAc+pPP2A reac" id="PKAcPP2AB56d--PKAc+pPP2A_id">
        <Reactant specieID="PKAcPP2AB56d"  />
        <Product  specieID="PKAc"           />
        <Product  specieID="pPP2A"          />

        <forwardRate> 0.0e-03         </forwardRate>
        <reverseRate> 0.0             </reverseRate>
    </Reaction>

    <!--pPP2A(_B56d)           ->  PP2AB56d           (in xpp: v28=0.004) -->
    <Reaction name = "pPP2A--PP2A reac" id="pPP2A--PP2Aid">
        <Reactant specieID="pPP2A"          />
        <Product  specieID="PP2AB56d"      />

        <forwardRate> 0.02e-03       </forwardRate>
        <reverseRate> 0.0             </reverseRate>
    </Reaction>

    <!--PP2ABPR72  + Ca         ->  PP2Acal(_BPR72)      (in xpp: kf4=0.022, kb4=0.11)  -->
    <!-- binding updated from paper measuring binding -->
    <Reaction name = "PP2ABPR72+Ca--PP2Acal reac" id="PP2Acal3+Ca--PP2Acal_id">
        <Reactant specieID="PP2ABPR72"         />
        <Reactant specieID="Ca"                 />
        <Product  specieID="PP2Acal"              />

        <forwardRate> 0.02e-6         </forwardRate>
        <reverseRate> 0.1e-3           </reverseRate>
    </Reaction>

    <!-- D32 + PKAc    <-> D32PKAc      Km=3.7uM    (in xpp: k20=0.0027 k_20=8 v20=2, Kd=) -->
    <Reaction name = "D32+PKAc--D32PKAc reac" id="D32+PKAc--D32PKAc_id">
        <Reactant specieID="D32"                    />
        <Reactant specieID="PKAc"                   />
        <Product  specieID="D32PKAc"                 />

        <forwardRate> 0.0027e-03      </forwardRate>
        <reverseRate> 8.0e-03         </reverseRate>
    </Reaction>

    <!-- D32PKAc            -> PKAc + D32p34  (in xpp: v20=2) -->
    <Reaction name = "D32PKAc--PKAc+D32p34 reac" id="D32PKAc--PKAc+D32p34_id">
        <Reactant specieID="D32PKAc"                 />
        <Product  specieID="PKAc"                   />
        <Product  specieID="D32p34"                   />

        <forwardRate> 0.0e-03         </forwardRate>
        <reverseRate> 0.0             </reverseRate>
    </Reaction>

    <!-- D32p34 + PP1    <-> D32p34PP1       (in xpp: k21=0.4 k_21=0.58, Kd=) -->
    <Reaction name = "D32p34+PP1--D32p34pp1 reac" id="D32p34+PP1--D32p34pp1_id">
        <Reactant specieID="D32p34"                   />
        <Reactant specieID="PP1"                    />
        <Product  specieID="D32p34PP1"                />

        <forwardRate> 0.4e-03         </forwardRate>
        <reverseRate> 0.58e-03        </reverseRate>
    </Reaction>

    <!-- ******* PP2B dephos of DARPP32 *********** -->
    <!-- D32p34 + PP2BCamCa4  <-> D32p34PP2BCamCa4   King et al. 1984 Km=1.6uM -->
    <Reaction name = "D32p34+PP2BCamCa4--D32p34PP2BCamCa4 reac" id="D32p34+PP2BCamCa4--D32p34PP2BCamCa4_id">
        <Reactant specieID="D32p34"                   />
        <Reactant specieID="PP2BCamCa4"             />
        <Product  specieID="D32p34PP2BCamCa4"         />

        <forwardRate> 4.0e-06       </forwardRate>
        <reverseRate> 4.0e-03         </reverseRate>
    </Reaction>

    <!-- D32p34PP2BCamCa4     -> D32 + PP2BCamCa4   King, Hemmings: Vmax =0.2-1/sec-->
    <Reaction name = "D32p34PP2BCamCa4--PP2BCamCa4+D32 reac" id="D32p34PP2BCamCa4--PP2BCamCa4+D32_id">
        <Reactant specieID="D32p34PP2BCamCa4"         />
        <Product  specieID="PP2BCamCa4"             />
        <Product  specieID="D32"                    />

        <forwardRate> 1e-03         </forwardRate>
        <reverseRate> 0.0             </reverseRate>
    </Reaction>

    <!-- D32p34PP1 + PP2BCamCa4    <-> D32p34PP1PP2BCamCa4  (in xpp: k36=0.001 k_36=2, Kd=2.5 uM) -->
    <Reaction name = "D32p34PP1+PP2BCamCa4--D32p34PP1PP2BCamCa4 reac" id="D32p34pp1+PP2BCamCa4--D32p34PP1PP2BCamCa4_id">
        <Reactant specieID="D32p34PP1"                />
        <Reactant specieID="PP2BCamCa4"             />
        <Product  specieID="D32p34PP1PP2BCamCa4"      />

        <forwardRate> 4.0e-06      </forwardRate>
        <reverseRate> 4.0e-03       </reverseRate>
    </Reaction>

    <!-- D32p34PP1PP2BCamCa4        -> PP1PP2BCamCa4  +  D32  (in xpp: v36=0.5) -->
    <Reaction name = "D32p34PP1PP2BCamCa4--PP1+PP2BCamCa4+D32 reac" id="D32p34PP1PP2BCamCa4--PP1+PP2BCamCa4+D32_id">
        <Reactant specieID="D32p34PP1PP2BCamCa4"      />
        <Product  specieID="PP2BCamCa4"             />
        <Product  specieID="PP1"                    />
        <Product  specieID="D32"                    />

        <forwardRate> 1e-03      </forwardRate>
        <reverseRate> 0.0             </reverseRate>
    </Reaction>

    <!--1/10th the activity compared to Ca4: Shifman ... Kennedy  PNAS 2006 (for CamKII)-->
    <Reaction name = "D32p34PP1+PP2BCamCa2C--D32p34PP1PP2BCamCa2C reac" id="D32p34pp1+PP2BCamCa2C--D32p34PP1PP2BCamCa2C_id">
        <Reactant specieID="D32p34PP1"                />
        <Reactant specieID="PP2BCamCa2C"             />
        <Product  specieID="D32p34PP1PP2BCamCa2C"      />

        <forwardRate> 0.10e-06      </forwardRate>
        <reverseRate> 0.40e-03       </reverseRate>
    </Reaction>

    <!-- D32p34PP1PP2BCamCa2C        -> PP1PP2BCamCa2C  +  D32  (in xpp: v36=0.5) -->
    <Reaction name = "D32p34PP1PP2BCamCa2C--PP1+PP2BCamCa2C+D32 reac" id="D32p34PP1PP2BCamCa2C--PP1+PP2BCamCa2C+D32_id">
        <Reactant specieID="D32p34PP1PP2BCamCa2C"      />
        <Product  specieID="PP2BCamCa2C"             />
        <Product  specieID="PP1"                    />
        <Product  specieID="D32"                    />

        <forwardRate> 0.1e-03      </forwardRate>
        <reverseRate> 0.0             </reverseRate>
    </Reaction>

    <!-- ******* PP2A dephos of DARPP32 *********** -->
    <!-- D32p34 + PP2ABPR72    <-> D32p34PP2ABPR72       (in xpp: k22b=0.0001 k_22b=2, Kd=) -->
    <!-- these are ~15x faster than xpp model, slower than Oliveira -->
    <!-- rates taken from StriatumCRCNS/StochasticSP1/PKAspace/MSPNreactionsPP2AslowPKAdiff.xml  -->
     <Reaction name = "D32p34+PP2ABPR72--D32p34PP2ABPR72 reac" id="D32p34+PP2ABPR72--D32p34PP2ABPR72_id">
        <Reactant specieID="D32p34"                   />
        <Reactant specieID="PP2ABPR72"             />
        <Product  specieID="D32p34PP2ABPR72"         />

        <forwardRate> 1.52e-06        </forwardRate>
        <reverseRate> 0.056           </reverseRate>
    </Reaction>

    <!-- D32p34PP2ABPR72            -> D32 + PP2ABPR72  (in xpp: v22b=0.5) -->
    <Reaction name = "D32p34PP2ABPR72--PP2ABPR72+D32 reac" id="D32p34PP2ABPR72--PP2ABPR72+D32_id">
        <Reactant specieID="D32p34PP2ABPR72"         />
        <Product  specieID="PP2ABPR72"             />
        <Product  specieID="D32"                    />

        <forwardRate> 0.014           </forwardRate>
        <reverseRate> 0.0             </reverseRate>
    </Reaction>

    <!-- D32p34 + PP2AB56d    <-> D32p34PP2AB56d       (in xpp: k22b=0.0001 k_22b=2, Kd=) -->
    <!-- these are ~15x faster than xpp model #######, slower than Oliveira -->
    <!-- rates taken from StriatumCRCNS/StochasticSP1/PKAspace/MSPNreactionsPP2AslowPKAdiff.xml  -->
    <Reaction name = "D32p34+PP2AB56d--D32p34PP2AB56d reac" id="D32p34+PP2AB56d--D32p34PP2AB56d_id">
        <Reactant specieID="D32p34"                   />
        <Reactant specieID="PP2AB56d"              />
        <Product  specieID="D32p34PP2AB56d"          />

        <forwardRate> 1.52e-06        </forwardRate>
        <reverseRate> 0.056           </reverseRate>
    </Reaction>

    <!-- D32p34PP2AB56d            -> D32 + PP2AB56d  (in xpp: v22b=0.5) -->
    <Reaction name = "D32p34PP2AB56d--PP2AB56d+D32 reac" id="D32p34PP2AB56d--PP2AB56d+D32_id">
        <Reactant specieID="D32p34PP2AB56d"          />
        <Product  specieID="PP2AB56d"              />
        <Product  specieID="D32"                    />

        <forwardRate> 0.014           </forwardRate>
        <reverseRate> 0.0             </reverseRate>
    </Reaction>

    <!-- D32p34pp1 + PP2ABPR72  <-> D32p34PP1PP2ABPR72 -> D32 + PP1 + PP2ABPR72  (in xpp: k36b=0.0001 k_36b=2, Kd=) -->
    <Reaction name = "D32p34pp1+PP2ABPR72--D32p34PP1PP2ABPR72 reac" id="D32p34pp1+PP2ABPR72--D32p34PP1PP2ABPR72_id">
        <Reactant specieID="D32p34PP1"                 />
        <Reactant specieID="PP2ABPR72"              />
        <Product  specieID="D32p34PP1PP2ABPR72"       />

        <forwardRate> 0.36e-06        </forwardRate>
        <reverseRate> 0.0146          </reverseRate>
    </Reaction>

    <!-- D32p34PP1PP2ABPR72          -> PP1PP2ABPR72 + D32 (in xpp: v36b=0.5) -->
    <Reaction name = "D32p34PP1PP2ABPR72--PP1+PP2ABPR72+D32 reac" id="D32p34PP1PP2ABPR72--PP1+PP2ABPR72+D32_id">
        <Reactant specieID="D32p34PP1PP2ABPR72"      />
        <Product  specieID="PP2ABPR72"             />
	<Product  specieID="PP1"                    />
        <Product  specieID="D32"                    />

        <forwardRate> 0.00336          </forwardRate>
        <reverseRate> 0.0             </reverseRate>
    </Reaction>

    <!-- D32p34pp1 + PP2AB56d  <-> D32p34PP1PP2AB56d -> D32 + PP1 + PP2AB56d   -->
    <Reaction name = "D32p34pp1+PP2AB56d--D32p34PP1PP2AB56d reac" id="D32p34pp1+PP2AB56d--D32p34PP1PP2AB56d_id">
        <Reactant specieID="D32p34PP1"                />
        <Reactant specieID="PP2AB56d"              />
        <Product  specieID="D32p34PP1PP2AB56d"       />

        <forwardRate> 0.36e-06        </forwardRate>
        <reverseRate> 0.0146          </reverseRate>
    </Reaction>

    <!-- D32p34PP1PP2AB56d          -> PP1PP2AB56d + D32 (in xpp: v36b=0.5) -->
    <Reaction name = "D32p34PP1PP2AB56d--PP1+PP2AB56d+D32 reac" id="D32p34PP1PP2AB56d--PP1+PP2AB56d+D32_id">
        <Reactant specieID="D32p34PP1PP2AB56d"       />
        <Product  specieID="PP2AB56d"              />
        <Product  specieID="PP1"                    />
        <Product  specieID="D32"                    />

        <forwardRate> 0.00336         </forwardRate>
        <reverseRate> 0.0             </reverseRate>
    </Reaction>

<!-- phos D32 on T75, which then inhibits PKAc -->
    <!-- Cdk5   +   D32  <->    Cdk5D32     (in xpp: k23=0.00045 k_23=2) -->
    <Reaction name = "Cdk5+D32--Cdk5D32 reac" id="Cdk5+D32--Cdk5D32_id">
        <Reactant specieID="Cdk5"               />
        <Reactant specieID="D32"                />
        <Product  specieID="Cdk5D32"            />

        <forwardRate> 0.0045e-03     </forwardRate>
        <reverseRate> 40e-3        </reverseRate>
    </Reaction>

    <!-- Cdk5D32        -> D32p75 + Cdk5 (in xpp: v23=0.5) -->
    <!-- rates and quantities adjusted to achieve 10 uM D32p75 at basal -->
    <Reaction name = "Cdk5D32--D32p75+Cdk5 reac" id="Cdk5D32--D32p75+Cdk5_id">
        <Reactant specieID="Cdk5D32"            />
        <Product  specieID="D32p75"               />
        <Product  specieID="Cdk5"               />

        <forwardRate> 10e-3         </forwardRate>
        <reverseRate> 0.0             </reverseRate>
    </Reaction>

    <!--D32p75  +  PKAc  <->  DP75PKA   (in xpp: k24=0.00037 k_24=1) Kd=2.7uM -->
    <Reaction name = "D32p75+PKAc--D32p75PKAc reac" id="D32p75+PKAc--D32p75PKAc_id">
        <Reactant specieID="D32p75"               />
        <Reactant specieID="PKAc"               />
        <Product  specieID="D32p75PKAc"               />

        <forwardRate> 0.00037e-03     </forwardRate>
        <reverseRate> 1.0e-03         </reverseRate>
    </Reaction>

<!-- dephos of D32p75 on PP2A(both BPR75 and B56d), phosphoPP2A, and Ca bound PP2A -->
    <!--D32p75 + pPP2A(_B56d) <-> D32p75pPP2A(_B56d)  (must faster than in xpp: k25=0.0004 k_25=12)-->
    <Reaction name = "D32p75+pPP2A--D32p75pPP2A reac" id="D32p75+pPP2A--D32p75pPP2Aid">
        <Reactant specieID="D32p75"           />
        <Reactant specieID="pPP2A"          />
        <Product  specieID="D32p75pPP2A"       />

        <forwardRate> 0.015e-03        </forwardRate>
        <reverseRate> 168e-3          </reverseRate>
    </Reaction>

    <!--D32p75pPP2A(_B56d)        -> D32  + pPP2A(_B56d) (in xpp: v25=3) -->
    <Reaction name = "D32p75pPP2A--D32+pPP2A reac" id="D32p75pPP2A--D32+pPP2Aid">
        <Reactant specieID="D32p75pPP2A"       />
        <Product  specieID="D32"            />
        <Product  specieID="pPP2A"          />

        <forwardRate> 42e-3           </forwardRate>
        <reverseRate> 0.0             </reverseRate>
    </Reaction>

    <!--D32p75 + PP2ABPR72 <-> D32p75PP2ABPR72   (much faster than in xpp: k26=0.0001 k_26=6.4) -->
     <Reaction name = "D32p75+PP2ABPR72--D32p75PP2ABPR72 reac" id="D32p75+PP2ABPR72--D32p75PP2ABPR72_id">
        <Reactant specieID="D32p75"                   />
        <Reactant specieID="PP2ABPR72"             />
        <Product  specieID="D32p75PP2ABPR72"         />

        <forwardRate> 0.0023e-3          </forwardRate>
        <reverseRate> 84e-3           </reverseRate>
    </Reaction>

    <!--D32p75PP2ABPR72        -> D32  + PP2ABPR72       (in xpp: v26=1.6) -->
    <Reaction name = "D32p75PP2ABPR72--D32+PP2ABPR72 reac" id="D32p75PP2ABPR72--D32+PP2ABPR72_id">
        <Reactant specieID="D32p75PP2ABPR72"         />
        <Product  specieID="D32"                    />
        <Product  specieID="PP2ABPR72"             />

        <forwardRate> 21e-3           </forwardRate>
        <reverseRate> 0.0             </reverseRate>
    </Reaction>

    <!--D32p75 + PP2AB56d <-> D32p75PP2AB56d   (must faster than in xpp: k26=0.0001 k_26=6.4) -->
     <Reaction name = "D32p75+PP2AB56d--D32p75PP2AB56d reac" id="D32p75+PP2AB56d--D32p75PP2AB56d_id">
        <Reactant specieID="D32p75"                   />
        <Reactant specieID="PP2AB56d"              />
        <Product  specieID="D32p75PP2AB56d"          />

        <forwardRate> 0.0023e-3          </forwardRate>
        <reverseRate> 84e-3           </reverseRate>
    </Reaction>

    <!--D32p75PP2AB56d        -> D32  + PP2AB56d       (in xpp: v26=1.6) -->
    <Reaction name = "D32p75PP2AB56d--D32+PP2AB56d reac" id="D32p75PP2AB56d--D32+PP2AB56d_id">
        <Reactant specieID="D32p75PP2AB56d"          />
        <Product  specieID="D32"                    />
        <Product  specieID="PP2AB56d"              />

        <forwardRate> 21e-3           </forwardRate>
        <reverseRate> 0.0             </reverseRate>
    </Reaction>

    <!--D32p75  +  PP2Acal(_BPR72) -> D32p75PP2Acal(_BPR72)  (must faster than in xpp: k25c=0.0004 k_25c=12 v25c=3) -->
     <Reaction name = "D32p75+PP2Acal--D32p75PP2Acal reac" id="D32p75+PP2Acal--D32p75PP2A_id">
        <Reactant specieID="D32p75"               />
        <Reactant specieID="PP2Acal"              />
        <Product  specieID="D32p75PP2Acal"           />

        <forwardRate> 0.015e-03        </forwardRate>
        <reverseRate> 168e-3           </reverseRate>
    </Reaction>

    <!--D32p75PP2Acal(_BPR72)  ->  D32 +  PP2Acal(_BPR72) -->
    <Reaction name = "D32p75PP2Acal-D32+PP2Acal reac" id="D32p75PP2Acal-D32+PP2Acal_id">
        <Reactant specieID="D32p75PP2Acal"           />
        <Product  specieID="PP2Acal"              />
        <Product  specieID="D32"                />

        <forwardRate> 42e-3           </forwardRate>
        <reverseRate> 0.0             </reverseRate>
    </Reaction>


    <!--XII. *************** CamKII ************* ReDo/simplify with higher order Rxn-->

  <!--1) CamCa4 + CK <-> CKCamCa4  -->
    <Reaction name = "CK bind" id="CK_bind">
        <Reactant specieID="CamCa4"                 />
        <Reactant specieID="CK"                     />
        <Product  specieID="CKCamCa4"               />

        <forwardRate> 0.01e-3   </forwardRate>
        <reverseRate> 3e-3      </reverseRate>
        <!--0.8 from ode file
	    reverseRate> 0.8e-3      </reverseRate-->
    </Reaction>

<!--2a) 3 CKCamCa4 + 1 CKCamCa4 <-> 3  CKCamCa4 + 1 CKpCamCa4-->
    <Reaction name = "CKCam bind" id="CKCam_bind">
        <Reactant specieID="CKCamCa4"  power="4"        />
        <Product  specieID="CKCamCa4"   power="3"         />
        <Product  specieID="CKpCamCa4"           />

        <forwardRate> 13.0e-18 </forwardRate>
        <reverseRate> 0e-3     </reverseRate>
    </Reaction>

<!--2b)  2 CKCamCa4 + 1 CKCamCa4 <-> 2 CKCamCa4 + 1 CKpCamCa4-->
    <Reaction name = "CKCam bind" id="CKCam_bind">
        <Reactant specieID="CKCamCa4"  power="3"        />
        <Product  specieID="CKCamCa4"  power="2"         />
        <Product  specieID="CKpCamCa4"           />

        <forwardRate> 2.0e-12 </forwardRate>
        <reverseRate> 0e-3     </reverseRate>
    </Reaction>

<!--2c)  2 CKpCamCa4 + 2 CKCamCa4 <-> 3 CKpCamCa4 + 1 CKCamCa4-->
    <Reaction name = "CKCam bind" id="CKCam_bind">
        <Reactant specieID="CKpCamCa4"  power="2"        />
        <Reactant specieID="CKCamCa4"  power="2"        />
        <Product  specieID="CKCamCa4"           />
        <Product  specieID="CKpCamCa4" power="3"         />

        <forwardRate> 27.1e-18 </forwardRate>
        <reverseRate> 0e-3     </reverseRate>
    </Reaction>

  <!-- CKpCamCamCa4 <-> CKp + CamCa4 -->
    <Reaction name = "CKp auto" id="CKp_auto">
        <Reactant specieID="CKpCamCa4"              />
        <Product  specieID="CamCa4"                 />
        <Product  specieID="CKp"                    />

        <forwardRate> 0.0008e-3 </forwardRate>
        <reverseRate> 0.01e-3   </reverseRate>
    </Reaction>

    <!-- CKp + PP1 <-> CKpPP1 -->
    <Reaction name = "CKp bind" id="CKp_bind">
        <Reactant specieID="CKp"                    />
        <Reactant specieID="PP1"                    />
        <Product  specieID="CKpPP1"                 />

        <forwardRate> 0.009e-06   </forwardRate>
        <reverseRate> 0.08e-03    </reverseRate>
    </Reaction>
 
    <!-- CKpPP1 -> PP1 + CK -->
    <Reaction name = "CKpPP1 reac" id="CKpPP1_reac">
        <Reactant specieID="CKpPP1"                 />
        <Product specieID="PP1"                     />
        <Product specieID="CK"                      />

        <forwardRate> 0.019e-03   </forwardRate>
        <reverseRate> 0.0         </reverseRate>
    </Reaction>

    <!-- CKpCamCa4 + PP1 <-> CKpCamCa4PP1 -->
    <Reaction name = "CKpCamCa4PP1_bind" id="CKpCamPP1_bind">
        <Reactant specieID="CKpCamCa4"              />
        <Reactant specieID="PP1"                    />
        <Product  specieID="CKpCamCa4PP1"           />

        <forwardRate> 0.0045e-06  </forwardRate>
        <reverseRate> 0.04e-03   </reverseRate>
    </Reaction>

<!--Dephos of CKpCamCa4 by PP1 -->
    <!-- CKpCamCa4PP1 -> PP1 + CKCamCa4 -->
    <Reaction name = "CKpCamCa4PP1_reac" id="CKpCamPP1_reac">
        <Reactant specieID="CKpCamCa4PP1"           />
        <Product  specieID="PP1"                    />
        <Product  specieID="CKCamCa4"               />

        <forwardRate> 0.0095e-3    </forwardRate>
        <reverseRate> 0.0         </reverseRate>
    </Reaction>

<!--2a)  CKCamCa4 + AIP <-> CKCamCa4_block, affinity = 40 nM-->
    <Reaction name = "CKCamblock" id="CKCamblock">
        <Reactant specieID="CKCamCa4"          />
        <Reactant specieID="AIP"          />
        <Product  specieID="CKCam_block"           />

        <forwardRate> 25e-6 </forwardRate>
        <reverseRate> 1e-3     </reverseRate>
    </Reaction>


<!-- ***************************************************************************-->
<!-- CaMKII phos of Dag Lipase to suppress 2ag during LTP: NOVEL REACTION -->
    <!--1a) Dgl + CKCam <-> Dgl_CKCam -->
    <Reaction name = "Dgl_CKCamCa4_bind" id="Dgl_CKCamCa4_bind">
        <Reactant specieID="Dgl"              />
        <Reactant specieID="CKCamCa4"           />
        <Product  specieID="Dgl_CKCamCa4"     />

        <forwardRate> 0.36e-6          </forwardRate>
        <reverseRate> 0.1e-3            </reverseRate>
    </Reaction>

    <!-- Dgl_CKCam -> pDgl + CKCam -->
    <Reaction name = "Dgl_CKCam_diss" id="Dgl_CKCam_diss">
        <Reactant specieID="Dgl_CKCamCa4"     />
        <Product  specieID="pDgl"         />
        <Product  specieID="CKCamCa4"           />

        <forwardRate> 0.025e-3            </forwardRate>
        <reverseRate> 0.0               </reverseRate>
    </Reaction>

    <!--2a Dgl + CKpCam <-> Dgl_CKpCam -->
    <Reaction name = "Dgl_CKpCamCa4_bind" id="Dgl_CKpCamCa4_bind">
        <Reactant specieID="Dgl"              />
        <Reactant specieID="CKpCamCa4"          />
        <Product  specieID="Dgl_CKpCamCa4"    />

        <forwardRate> 5.4e-6          </forwardRate>
        <reverseRate> 1.5e-3          </reverseRate>
    </Reaction>

    <!-- Dgl_CKpCam -> pDgl + CKpCam -->
    <Reaction name = "Dgl_CKpCamCa4_diss" id="Dgl_CKpCamCa4_diss">
        <Reactant specieID="Dgl_CKpCamCa4"    />
        <Product  specieID="pDgl"         />
        <Product  specieID="CKpCamCa4"          />

        <forwardRate> 0.375e-3        </forwardRate>
        <reverseRate> 0.0               </reverseRate>
    </Reaction>

    <!--1b) CaDgl + CKCam <-> Dgl_CKCam -->
    <!--Reaction name = "CaDgl_CKCamCa4_bind" id="CaDgl_CKCamCa4_bind">
        <Reactant specieID="CaDgl"              />
        <Reactant specieID="CKCamCa4"           />
        <Product  specieID="CaDgl_CKCamCa4"     />

        <forwardRate> 0.36e-6          </forwardRate>
        <reverseRate> 0.1e-3            </reverseRate>
    </Reaction-->

    <!-- CaDgl_CKCam -> CapDgl + CKCam -->
    <!--Reaction name = "CaDgl_CKCam_diss" id="CaDgl_CKCam_diss">
        <Reactant specieID="CaDgl_CKCamCa4"     />
        <Product  specieID="CapDgl"         />
        <Product  specieID="CKCamCa4"           />

        <forwardRate> 0.025e-3            </forwardRate>
        <reverseRate> 0.0               </reverseRate>
    </Reaction-->

    <!--2b CaDgl + CKpCam <-> CaDgl_CKpCam -->
    <Reaction name = "CaDgl_CKpCamCa4_bind" id="CaDgl_CKpCamCa4_bind">
        <Reactant specieID="CaDgl"              />
        <Reactant specieID="CKpCamCa4"          />
        <Product  specieID="CaDgl_CKpCamCa4"    />

        <forwardRate> 5.4e-6          </forwardRate>
        <reverseRate> 1.5e-3          </reverseRate>
    </Reaction>

    <!-- CaDgl_CKpCam -> CapDgl + CKpCam -->
    <Reaction name = "CaDgl_CKpCamCa4_diss" id="CaDgl_CKpCamCa4_diss">
        <Reactant specieID="CaDgl_CKpCamCa4"    />
        <Product  specieID="CapDgl"         />
        <Product  specieID="CKpCamCa4"          />

        <forwardRate> 0.375e-3        </forwardRate>
        <reverseRate> 0.0               </reverseRate>
    </Reaction>

    <!-- 3)Dgl + CKp <-> Dgl_CKp -->
    <Reaction name = "Dgl_CKp_bind" id="Dgl_CKp_bind">
        <Reactant specieID="Dgl"              />
        <Reactant specieID="CKp"                />
        <Product  specieID="Dgl_CKp"          />

        <forwardRate> 0.36e-6          </forwardRate>
        <reverseRate> 0.1e-3            </reverseRate>
    </Reaction>

    <!-- Dgl_CKp -> pDgl + CKp -->
    <Reaction name = "Dgl_CKp_diss" id="Dgl_CKp_diss">
        <Reactant specieID="Dgl_CKp"          />
        <Product  specieID="pDgl"         />
        <Product  specieID="CKp"                />

        <forwardRate> 0.025e-3            </forwardRate>
        <reverseRate> 0.0               </reverseRate>
    </Reaction>

    <!-- pDgl dephosphorylation -->
    <Reaction name = "pDgl_dephos" id="pDgl_dephos">
        <Reactant specieID="pDgl"         />
        <Product  specieID="Dgl"           />

        <forwardRate> 0.1e-3            </forwardRate>
        <reverseRate> 0.0               </reverseRate>
    </Reaction>

    <!-- AKAR3 rates to allow comparison to Castro, etc. -->
     <Reaction name = "AKAR3+PKAc bind" >
        <Reactant specieID="AKAR3"            />
        <Reactant  specieID="PKAc"               />
        <Product  specieID="PKAcAKAR3"            />

        <forwardRate> 0.00625e-03     </forwardRate>
        <reverseRate> 0.75e-03    </reverseRate>
    </Reaction>

    <Reaction name = "PKAcAKAR3 phos" >
       <Reactant specieID="PKAcAKAR3"            />
        <Product  specieID="PKAc"               />
        <Product  specieID="pAKAR3"            />

        <forwardRate> 0.1875e-03     </forwardRate>
        <reverseRate> 0e-03    </reverseRate>
    </Reaction>

     <Reaction name = "pAKAR3+PP1 bind" >
        <Reactant specieID="pAKAR3"            />
        <Reactant  specieID="PP1"               />
        <Product  specieID="PP1pAKAR3"            />

        <forwardRate> 0.00025e-03     </forwardRate>
        <reverseRate> 1.2e-03    </reverseRate>
    </Reaction>

    <Reaction name = "PP1pAKAR3 dephos" >
       <Reactant specieID="PP1pAKAR3"            />
        <Product  specieID="PP1"               />
        <Product  specieID="AKAR3"            />

        <forwardRate> 0.312e-03     </forwardRate>
        <reverseRate> 0e-03    </reverseRate>
    </Reaction>
<!-- ############### Inhibition of phosphatases by specific antagonists  ###################-->
  <!-- cyclosporin A inhibits PP2A 32 pM (0.1-1nM according to Tocris)-->
  <Reaction name="OAblockB56" id="OAblockB56">
    <Reactant specieID="OA"/>
    <Reactant specieID="PP2AB56d"/>
    <Product specieID="OA_PP2AB56d"/>

	<forwardRate>0.005e-3</forwardRate>
	<reverseRate>0.00015e-3</reverseRate>
  </Reaction>
  <Reaction name="OAblockB56pp" id="OAblockB56p">
    <Reactant specieID="OA"/>
    <Reactant specieID="pPP2A"/>
    <Product specieID="OA_pPP2A"/>
	<forwardRate>0.005e-3</forwardRate>
	<reverseRate>0.00015e-3</reverseRate>

  </Reaction>
  <Reaction name="OAblockBPR" id="OAblockBPR">
    <Reactant specieID="OA"/>
    <Reactant specieID="PP2ABPR72"/>
    <Product specieID="OA_PP2ABPR72"/>
	<forwardRate>0.005e-3</forwardRate>
	<reverseRate>0.00015e-3</reverseRate>

  </Reaction>
  <Reaction name="OAblock2BPRal" id="OAblockBPRcal">
    <Reactant specieID="OA"/>
    <Reactant specieID="PP2Acal"/>
    <Product specieID="OA_PP2Acal"/>
	<forwardRate>0.005e-3</forwardRate>
	<reverseRate>0.00015e-3</reverseRate>

  </Reaction>
  <!-- Okadaic acid inhibits PP1 150 nM Kd-->
  <Reaction name="OAblock1" id="OAblock1">
    <Reactant specieID="OA"/>
    <Reactant specieID="PP1"/>
    <Product specieID="OA_PP1"/>

	<forwardRate>0.001e-3</forwardRate>
	<reverseRate>0.15e-3</reverseRate>
   </Reaction>

   <!-- Rolipram IC50=2.0, Papaverine IC50=17nM -->
    <Reaction name = "PDE4 inhib" id="PDE4inhib">
        <Reactant specieID="PDE4"           />
        <Reactant specieID="Roli"            />
        <Product  specieID="RoliPDE4"       />
        <forwardRate>0.001e-03  </forwardRate>
        <reverseRate>2e-03    </reverseRate>
    </Reaction>

    <Reaction name = "PDE10 inhib" id="PDE10inhib">
        <Reactant specieID="PDE10"           />
        <Reactant specieID="Pap"            />
        <Product  specieID="PapPDE10"       />
        <forwardRate>0.001e-03  </forwardRate>
        <reverseRate>0.017e-03    </reverseRate>
    </Reaction>

   <!--block of m1R IC50 is 0.94 nM -->
      <Reaction name = "telenz+m1R--telenzm1R" id="telenz+m1R--telenzm1R">
        <Reactant specieID="telenz"              />
        <Reactant specieID="m1R"              />
        <Product  specieID="telenzm1R"         />

        <forwardRate> 0.95e-03 </forwardRate>
        <reverseRate> 2.5e-03      </reverseRate>
    </Reaction>

   <Reaction name = "telenz+m1RGq- -telenzm1RGq" id="telenz+m1RGq- -telenzm1RGq">
        <Reactant specieID="telenz" />
        <Reactant specieID="m1RGq" />
        <Product specieID="telenzm1RGq" />

        <forwardRate> 39.6e-03 </forwardRate>
        <reverseRate> 2.5e-03        </reverseRate>
   </Reaction>

   <!-- block of M4R IC50 is 91 nM -->
   <Reaction name = "PD1028+m4R--PD1028m4R" id="PD1028+m4R--PD1028m4R">
        <Reactant specieID="PD1028"              />
        <Reactant specieID="m4R"              />
        <Product  specieID="PD1028m4R"         />

        <forwardRate> 0.028e-03 </forwardRate>
        <reverseRate> 2.5e-03      </reverseRate>
    </Reaction>

    <Reaction name = "Gim4R+PD1028--PD1028m4RGi" id="Gm4R+PD1028--PD1028m4RGi">
        <Reactant specieID="Gim4R"                     />
        <Reactant specieID="PD1028"                      />
        <Product  specieID="PD1028m4RGi"                    />

        <forwardRate> 3.024e-03 </forwardRate>
        <reverseRate> 20.0e-03        </reverseRate>
    </Reaction>

</ReactionScheme>

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