Neuronal dendrite calcium wave model (Neymotin et al, 2015)

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Accession:168874
"... We developed a reaction-diffusion model of an apical dendrite with diffusible inositol triphosphate (IP3 ), diffusible Ca2+, IP3 receptors (IP3 Rs), endoplasmic reticulum (ER) Ca2+ leak, and ER pump (SERCA) on ER. ... At least two modes of Ca2+ wave spread have been suggested: a continuous mode based on presumed relative homogeneity of ER within the cell; and a pseudo-saltatory model where Ca2+ regeneration occurs at discrete points with diffusion between them. We compared the effects of three patterns of hypothesized IP3 R distribution: 1. continuous homogeneous ER, 2. hotspots with increased IP3R density (IP3 R hotspots), 3. areas of increased ER density (ER stacks). All three modes produced Ca2+ waves with velocities similar to those measured in vitro (~50 - 90µm /sec). ... The measures were sensitive to changes in density and spacing of IP3 R hotspots and stacks. ... An extended electrochemical model, including voltage gated calcium channels and AMPA synapses, demonstrated that membrane priming via AMPA stimulation enhances subsequent Ca2+ wave amplitude and duration. Our modeling suggests that pharmacological targeting of IP3 Rs and SERCA could allow modulation of Ca2+ wave propagation in diseases where Ca2+ dysregulation has been implicated. "
Reference:
1 . Neymotin SA, McDougal RA, Sherif MA, Fall CP, Hines ML, Lytton WW (2015) Neuronal calcium wave propagation varies with changes in endoplasmic reticulum parameters: a computer model. Neural Comput 27:898-924 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Dendrite;
Brain Region(s)/Organism:
Cell Type(s): Hippocampus CA1 pyramidal GLU cell; Hippocampus CA3 pyramidal GLU cell; Neocortex V1 L6 pyramidal corticothalamic GLU cell; Neocortex V1 L2/6 pyramidal intratelencephalic GLU cell;
Channel(s): I T low threshold; I A; I K; I K,Ca; I CAN; I Sodium; I Calcium; I_SERCA; I_KD; Ca pump;
Gap Junctions:
Receptor(s): AMPA;
Gene(s):
Transmitter(s): Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Calcium waves; Reaction-diffusion;
Implementer(s): Neymotin, Sam [samn at neurosim.downstate.edu]; McDougal, Robert [robert.mcdougal at yale.edu]; Sherif, Mohamed [mohamed.sherif.md at gmail.com];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; Hippocampus CA3 pyramidal GLU cell; Neocortex V1 L6 pyramidal corticothalamic GLU cell; Neocortex V1 L2/6 pyramidal intratelencephalic GLU cell; AMPA; I T low threshold; I A; I K; I K,Ca; I CAN; I Sodium; I Calcium; I_SERCA; I_KD; Ca pump; Glutamate;
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ca1dDemo
data
readme.txt
cagk.mod *
cal_mig.mod
can_mig.mod
cat_mig.mod
kaprox.mod *
kdrca1.mod *
km.mod *
misc.mod *
na3n.mod *
naf.mod
NMDA.mod
stats.mod *
vecst.mod *
AMPA0.cfg
AMPA150.cfg
analysisCode.py
batch.py
cawave.cfg
cawave.py
conf.py
geneval_cvode.inc *
misc.h *
netcon.inc *
nqs.hoc
nqs.py
plot_fig11.py
setup.hoc *
vector.py *
                            
TITLE K-A channel from Klee Ficker and Heinemann
: modified to account for Dax A Current --- M.Migliore Jun 1997
: modified to be used with cvode  M.Migliore 2001

UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)

}

PARAMETER {
	sh = 6
	v (mV)
	celsius		(degC)
	gkabar=.008 (mho/cm2)
        vhalfn=11   (mV)
        vhalfl=-56   (mV)
        a0l=0.05      (/ms)
        a0n=0.05    (/ms)
        zetan=-1.5    (1)
        zetal=3    (1)
        gmn=0.55   (1)
        gml=1   (1)
	lmin=2  (mS)
	nmin=0.1  (mS)
	pw=-1    (1)
	tq=-40
	qq=5
	q10=5
	qtl=1
	ek
}


NEURON {
	SUFFIX kap
	USEION k READ ek WRITE ik
        RANGE gkabar,gka, sh
        GLOBAL ninf,linf,taul,taun,lmin
}

STATE {
	n
        l
}

ASSIGNED {
	ik (mA/cm2)
        ninf
        linf      
        taul
        taun
        gka
}

INITIAL {
	rates(v)
	n=ninf
	l=linf
}


BREAKPOINT {
	SOLVE states METHOD cnexp
	gka = gkabar*n*l
	ik = gka*(v-ek)

}


FUNCTION alpn(v(mV)) {
LOCAL zeta
  zeta=zetan+pw/(1+exp((v-tq-sh)/qq))
  alpn = exp(1.e-3*zeta*(v-vhalfn-sh)*9.648e4/(8.315*(273.16+celsius))) 
}

FUNCTION betn(v(mV)) {
LOCAL zeta
  zeta=zetan+pw/(1+exp((v-tq-sh)/qq))
  betn = exp(1.e-3*zeta*gmn*(v-vhalfn-sh)*9.648e4/(8.315*(273.16+celsius))) 
}

FUNCTION alpl(v(mV)) {
  alpl = exp(1.e-3*zetal*(v-vhalfl-sh)*9.648e4/(8.315*(273.16+celsius))) 
}

FUNCTION betl(v(mV)) {
  betl = exp(1.e-3*zetal*gml*(v-vhalfl-sh)*9.648e4/(8.315*(273.16+celsius))) 
}

DERIVATIVE states {     : exact when v held constant; integrates over dt step
        rates(v)
        n' = (ninf - n)/taun
        l' =  (linf - l)/taul
}

PROCEDURE rates(v (mV)) { :callable from hoc
        LOCAL a,qt
        qt=q10^((celsius-24)/10)
        a = alpn(v)
        ninf = 1/(1 + a)
        taun = betn(v)/(qt*a0n*(1+a))
	if (taun<nmin) {taun=nmin}
        a = alpl(v)
        linf = 1/(1+ a)
	taul = 0.26*(v+50-sh)/qtl
	if (taul<lmin/qtl) {taul=lmin/qtl}
}















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