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]
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 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 [Samuel.Neymotin at nki.rfmh.org]; 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 T-calcium channel
: T-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)
	(molar) = (1/liter)
	(mM) = (millimolar)

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

PARAMETER {
	v (mV)
	celsius = 25	(degC)
	gcatbar=.003 (mho/cm2)
	cai = 50.e-6 (mM)
	cao = 2 (mM)
	q10 = 5
	mmin=0.2
	hmin=10
	a0h =0.015
	zetah = 3.5
	vhalfh = -75
	gmh=0.6	
	a0m =0.04
	zetam = 2
	vhalfm = -28
	gmm=0.1	
}


NEURON {
	SUFFIX cat
	USEION ca READ cai,cao WRITE ica
        RANGE gcatbar, ica, gcat
        GLOBAL hinf,minf,mtau,htau
}

STATE {
	m h 
}

ASSIGNED {
	ica (mA/cm2)
        gcat (mho/cm2)
	hinf
	htau
	minf
	mtau
}

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

BREAKPOINT {
	SOLVE states METHOD cnexp
	gcat = gcatbar*m*m*h
	ica = gcat*ghk(v,cai,cao)

}

DERIVATIVE states {	: exact when v held constant
	rates(v)
	m' = (minf - m)/mtau
	h' = (hinf - h)/htau
}


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 = exp(0.0378*zetah*(v-vhalfh)) 
}

FUNCTION beth(v(mV)) {
  beth = exp(0.0378*zetah*gmh*(v-vhalfh)) 
}

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

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

PROCEDURE rates(v (mV)) { :callable from hoc
	LOCAL a,b, qt
        qt=q10^((celsius-25)/10)

	a = 0.2*(-1.0*v+19.26)/(exp((-1.0*v+19.26)/10.0)-1.0)
	b = 0.009*exp(-v/22.03)
	minf = a/(a+b)
	mtau = betmt(v)/(qt*a0m*(1+alpmt(v)))
	if (mtau<mmin) {mtau=mmin}

	a = 1.e-6*exp(-v/16.26)
	b = 1/(exp((-v+29.79)/10.)+1.)
	hinf = a/(a+b)
	htau = beth(v)/(qt*a0h*(1+alph(v)))
	if (htau<hmin) {htau=hmin}
}