Pleiotropic effects of SCZ-associated genes (Mäki-Marttunen et al. 2017)

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Accession:187615
Python and MATLAB scripts for studying the dual effects of SCZ-related genes on layer 5 pyramidal cell firing and sinoatrial node cell pacemaking properties. The study is based on two L5PC models (Hay et al. 2011, Almog & Korngreen 2014) and SANC models (Kharche et al. 2011, Severi et al. 2012).
Reference:
1 . Mäki-Marttunen T, Lines GT, Edwards AG, Tveito A, Dale AM, Einevoll GT, Andreassen OA (2017) Pleiotropic effects of schizophrenia-associated genetic variants in neuron firing and cardiac pacemaking revealed by computational modeling. Transl Psychiatry 7:5 [PubMed]
Citations  Citation Browser
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism:
Cell Type(s): Neocortex L5/6 pyramidal GLU cell; Cardiac atrial cell;
Channel(s): I Na,p; I Na,t; I L high threshold; I T low threshold; I A; I K; I M; I h; I K,Ca; I Sodium; I Calcium; I Potassium; I A, slow; Na/Ca exchanger; I_SERCA; Na/K pump; Kir;
Gap Junctions:
Receptor(s):
Gene(s): Nav1.1 SCN1A; Cav3.3 CACNA1I; Cav1.3 CACNA1D; Cav1.2 CACNA1C;
Transmitter(s):
Simulation Environment: NEURON; MATLAB; Python;
Model Concept(s): Schizophrenia;
Implementer(s): Maki-Marttunen, Tuomo [tuomo.maki-marttunen at tut.fi];
Search NeuronDB for information about:  Neocortex L5/6 pyramidal GLU cell; I Na,p; I Na,t; I L high threshold; I T low threshold; I A; I K; I M; I h; I K,Ca; I Sodium; I Calcium; I Potassium; I A, slow; Na/Ca exchanger; I_SERCA; Na/K pump; Kir;
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pleiotropy
almog
cells
BK.mod *
ca_h.mod
ca_r.mod
cad.mod *
epsp.mod *
ih.mod *
kfast.mod
kslow.mod
na.mod
SK.mod *
best.params *
calcifcurves.py
calcsteadystate.py
cc_run.hoc *
collectfig1.py
collectfig2.py
fig1_curves.mat
fig2_curves.mat
findDCshortthreshold.py
main.hoc *
model.hoc *
mosinit.hoc *
mutation_stuff.py
myrun.hoc *
mytools.py *
params.hoc *
runme.sh *
scalings.sav
                            
TITLE High threshold calcium current


INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}

NEURON {
	SUFFIX cah
	USEION ca READ cai,cao WRITE ica
	RANGE pbar, ica, minf, taum, hinf, tauh, shift, shifth
	GLOBAL qm, qh
}

UNITS {
	(molar) = (1/liter)
	(mV) =	(millivolt)
	(mA) =	(milliamp)
	(mM) =	(millimolar)

	FARADAY = (faraday) (coulomb)
	R = (k-mole) (joule/degC)
}

PARAMETER {
	v		(mV)
	celsius		(degC)
	pbar	=.2e-3	(cm/s)	: Maximum Permeability
	shift	= 2 	(mV)	: corresponds to 2mM ext Ca++
	shifth	= 0     (mV)	: inactivation shift
	cai	  (mM) :	adjusted for eca=120 mV
	cao		(mM)
	qm	= 4		: q10's for activation and inactivation
	qh	= 2		: from Coulter et al., J Physiol 414: 587, 1989

	offm = -14.17
	offh = -22.63
	offmt = -26.31
	offht = 19.73
	slom = 9.76
	sloh = 6.6
	slomt = 31.25
	sloht = 21.2765957
	taummax = 0.97
	tauhmax = 70
	mmax = 1.092
	mmin = 0.75

}

STATE {
	m h
}

ASSIGNED {
	ica	(mA/cm2)
	minf
	taum	(ms)
	hinf
	tauh	(ms)
	phim
	phih
}

BREAKPOINT {
	SOLVE castate METHOD cnexp
	ica = pbar * m*m*h * ghk(v, cai, cao)
}

DERIVATIVE castate {
	evaluatefct(v)

	m' = (minf - m) / taum
	h' = (hinf - h) / tauh
}


UNITSOFF
INITIAL {
	phim = qm ^ ((celsius-24)/10)
	phih = qh ^ ((celsius-24)/10)

	evaluatefct(v)

	m = minf
	h = hinf
}

PROCEDURE evaluatefct(v(mV)) {

	minf = mmax/(1+exp((offm-(v+shift))/slom))
	hinf = mmin/(1+exp(-(offh-(v+shifth))/sloh))

	taum = (taummax/(cosh(-(offmt-(v+shift))/slomt)))/phim
	tauh = (tauhmax/(cosh(-(offht-(v+shifth))/sloht)))/phih
	
}

FUNCTION ghk(v(mV), ci(mM), co(mM)) (.001 coul/cm3) {
	LOCAL z, eci, eco
	z = (1e-3)*2*FARADAY*v/(R*(celsius+273.15))
	eco = co*efun(z)
	eci = ci*efun(-z)
	:high cao charge moves inward
	:negative potential charge moves inward
	ghk = (.001)*2*FARADAY*(eci - eco)
}

FUNCTION efun(z) {
	if (fabs(z) < 1e-4) {
		efun = 1 - z/2
	}else{
		efun = z/(exp(z) - 1)
	}
}
FUNCTION nongat(v,cai,cao) {	: non gated current
	nongat = pbar * ghk(v, cai, cao)
}
UNITSON