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Compartmental differences in cAMP signaling pathways in hippocam. CA1 pyr. cells (Luczak et al 2017)

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Accession:245529
Model of cAMP signaling pathways in hippocampal CA1 pyramidal neurons investigate mechanisms underlying the experimentally observed difference in cAMP and PKA FRET between proximal and distal dendrites. Simulations show that compartmental difference in PKA activity required enrichment of protein phosphatase in small compartments; neither reduced PKA subunits nor increased PKA substrates were sufficient.
Reference:
1 . Luczak V, Blackwell KT, Abel T, Girault JA, Gervasi N (2017) Dendritic diameter influences the rate and magnitude of hippocampal cAMP and PKA transients during ß-adrenergic receptor activation. Neurobiol Learn Mem 138:10-20 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Molecular Network;
Brain Region(s)/Organism: Hippocampus; Mouse;
Cell Type(s): Hippocampus CA1 pyramidal GLU cell;
Channel(s):
Gap Junctions:
Receptor(s): Adrenergic;
Gene(s):
Transmitter(s): Norephinephrine;
Simulation Environment:
Model Concept(s): G-protein coupled; Influence of Dendritic Geometry; Reaction-diffusion;
Implementer(s): Blackwell, Avrama [avrama at gmu.edu];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; Adrenergic; Norephinephrine; 
<InitialConditions>

  <ConcentrationSet region="dend">
    <!-- calcium interacting proteins -->
        <NanoMolarity specieID="Ca"           value="60"/>
	<!-- total calbindin = 160 uM -->
        <NanoMolarity specieID="Calbin"       value="159980"/>
        <NanoMolarity specieID="CalbinC"      value="20"/>

	<!-- total calmodulin = 9000 nM (multiple AC bound by (4/3)-->
      	<NanoMolarity specieID="Cam"          value="3785"/>
      	<NanoMolarity specieID="CamCa2C"      value="130"/>
      	<NanoMolarity specieID="CamCa2N"      value="20"/>
      	<NanoMolarity specieID="CamCa4"       value="0"/>
	
<!-- total PP2B = 5000 nM--> 
        <NanoMolarity specieID="PP2B"                 value="96" />
        <NanoMolarity specieID="PP2BCam"              value="3482" />
        <NanoMolarity specieID="PP2BCamCa2C"          value="1251" />
        <NanoMolarity specieID="PP2BCamCa2N"          value="161" />
        <NanoMolarity specieID="PP2BCamCa4"           value="10" />

    <NanoMolarity specieID="L"            value="2.0"/>
    <NanoMolarity specieID="ATP"          value="1998000.0"/>
    <NanoMolarity specieID="cAMP"         value="89.0"/>
    <NanoMolarity specieID="AMP"          value="0.0"/>
    <NanoMolarity specieID="Epac1cAMP"    value="35.0"/>
    <NanoMolarity specieID="Epac1"        value="1965.0"/>
     <!--2200 PDE4 in both size morphologies 2068,66,0,62,4-->
    <NanoMolarity specieID="PDE4"         value="1359.0"/>
    <NanoMolarity specieID="pPDE4"        value="20.0"/>
    <NanoMolarity specieID="PKAcPDE4"     value="0.0"/>
    <NanoMolarity specieID="PDE4cAMP"     value="31.0"/>
    <NanoMolarity specieID="pPDE4cAMP"    value="0.0"/>
    
    <NanoMolarity specieID="PKAc" value="0.0"/>
    <NanoMolarity specieID="X" value="9970.0"/>
    <NanoMolarity specieID="pX" value="30.0"/>
<!-- total I1 = 1500, total PP1= 3500 -->
    <NanoMolarity specieID="I1" value="835.0"/>
    <NanoMolarity specieID="I1PKAc" value="0.0"/>
    <NanoMolarity specieID="Ip35" value="7.0"/>
    <NanoMolarity specieID="Ip35PP1" value="658.0"/>
    <NanoMolarity specieID="Ip35PP1PP2BCaMCa4" value="0.0"/>
    <NanoMolarity specieID="PP1" value="2842.0"/>
 </ConcentrationSet>
 
  <SurfaceDensitySet region="dend">
    <!--Gtot=3600, Rtot=600-->
    <PicoSD specieID="R"      value="3.0"/>
    <PicoSD specieID="LR"     value="0.0"/>
    <PicoSD specieID="Gs"     value="2911.0"/>
    <PicoSD specieID="GsR"    value="596.0"/>
    <PicoSD specieID="LRGs"   value="1.0"/>
    <PicoSD specieID="pLRGs"  value="0.0"/>
    <PicoSD specieID="GasGTP" value="3.0"/>
    <PicoSD specieID="GasGDP" value="0.0"/>
    <PicoSD specieID="Gbg"    value="92.0"/>

    <PicoSD specieID="PKA"      value="1234.0"/>
    <PicoSD specieID="PKAr"     value="0.0"/>
    <PicoSD specieID="PKAcAMP2" value="672.0"/>
    <PicoSD specieID="PKAcAMP4" value="94.0"/>
    <!--1700 AC in small dend, 70 AC5 -->
    <PicoSD specieID="AC1"               value="1510.0"/>
    <PicoSD specieID="AC1GasGTP"         value="68.0"/>
    <PicoSD specieID="AC1CamCa4"         value="7.0"/>
    <PicoSD specieID="AC1GasCamCa4"      value="0.0"/>
    <PicoSD specieID="AC1CamCa4ATP"      value="111.0"/>
    <PicoSD specieID="AC1GasCamCa4ATP"   value="4.0"/>
    <PicoSD specieID="AC5"               value="53" />
    <PicoSD specieID="AC5Gas"            value="2" />
    <PicoSD specieID="AC5GasATP"         value="15" />

</SurfaceDensitySet>
</InitialConditions>

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