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 Computation 27(4):898-924 [PubMed]
Citations  Citation Browser
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 cell; Hippocampus CA3 pyramidal cell; Neocortex V1 L6 pyramidal corticothalamic cell; Neocortex V1 L2/6 pyramidal intratelencephalic 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 cell; Hippocampus CA3 pyramidal cell; Neocortex V1 L6 pyramidal corticothalamic cell; Neocortex V1 L2/6 pyramidal intratelencephalic 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 n-calcium channel
: n-type calcium channel
: MODELDB 126814 CA3 by Safiulina et al - http://senselab.med.yale.edu/modeldb/ShowModel.asp?model=126814
: by Michele Migliore


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

	FARADAY = 96520 (coul)
	R = 8.3134 (joule/degC)
	KTOMV = .0853 (mV/degC)
}

PARAMETER {
	v (mV)
	celsius 		(degC)
	gcanbar=.0003 (mho/cm2)
	ki=.001 (mM)
	cai=50.e-6 (mM)
	cao = 2  (mM)
	q10=5
	mmin = 0.2
	hmin = 3
	a0m =0.03
	zetam = 2
	vhalfm = -14
	gmm=0.1	
}


NEURON {
	SUFFIX can
	USEION ca READ cai,cao WRITE ica
        RANGE gcanbar, ica, gcan       
        GLOBAL hinf,minf,taum,tauh
}

STATE {
	m h 
}

ASSIGNED {
	ica (mA/cm2)
        gcan  (mho/cm2) 
        minf
        hinf
        taum
        tauh
}

INITIAL {
        rates(v)
        m = minf
        h = hinf
}

BREAKPOINT {
	SOLVE states METHOD cnexp
	gcan = gcanbar*m*m*h*h2(cai)
	ica = gcan*ghk(v,cai,cao)

}

UNITSOFF
FUNCTION h2(cai(mM)) {
	h2 = ki/(ki+cai)
}


FUNCTION ghk(v(mV), ci(mM), co(mM)) (mV) {
        LOCAL nu,f

        f = KTF(celsius)/2
        nu = v/f
        ghk=-f*(1. - (ci/co)*exp(nu))*efun(nu)
}

FUNCTION KTF(celsius (degC)) (mV) {
        KTF = ((25./293.15)*(celsius + 273.15))
}


FUNCTION efun(z) {
	if (fabs(z) < 1e-4) {
		efun = 1 - z/2
	}else{
		efun = z/(exp(z) - 1)
	}
}

FUNCTION alph(v(mV)) {
	alph = 1.6e-4*exp(-v/48.4)
}

FUNCTION beth(v(mV)) {
	beth = 1/(exp((-v+39.0)/10.)+1.)
}

FUNCTION alpm(v(mV)) {
	alpm = 0.1967*(-1.0*v+19.88)/(exp((-1.0*v+19.88)/10.0)-1.0)
}

FUNCTION betm(v(mV)) {
	betm = 0.046*exp(-v/20.73)
}

FUNCTION alpmt(v(mV)) {
  alpmt = exp(0.0378*zetam*(v-vhalfm)) 
}

FUNCTION betmt(v(mV)) {
  betmt = exp(0.0378*zetam*gmm*(v-vhalfm)) 
}

UNITSON

DERIVATIVE states {     : exact when v held constant; integrates over dt step
        rates(v)
        m' = (minf - m)/taum
        h' = (hinf - h)/tauh
}

PROCEDURE rates(v (mV)) { :callable from hoc
        LOCAL a, b, qt
        qt=q10^((celsius-25)/10)
        a = alpm(v)
        b = 1/(a + betm(v))
        minf = a*b
	taum = betmt(v)/(qt*a0m*(1+alpmt(v)))
	if (taum<mmin/qt) {taum=mmin/qt}
        a = alph(v)
        b = 1/(a + beth(v))
        hinf = a*b
:	tauh=b/qt
	tauh= 80
	if (tauh<hmin) {tauh=hmin}
}