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]
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
hay
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calcifcurves.py
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collectfig2.py
fig1_curves.mat
fig2_curves.mat
findDCshortthreshold.py
mutation_stuff.py *
mytools.py *
runme.sh *
scalings_cs.sav
                            
:Comment : LVA ca channel. Note: mtau is an approximation from the plots
:Reference : :		Avery and Johnston 1996, tau from Randall 1997
:Comment: shifted by -10 mv to correct for junction potential
:Comment: corrected rates using q10 = 2.3, target temperature 34, orginal 21

NEURON	{
	SUFFIX Ca_LVAst
	USEION ca READ eca WRITE ica
	RANGE gCa_LVAstbar, gCa_LVAst, ica, offma, offmt, offha, offht, sloma, slomt, sloha, sloht, taummin, taumdiff, tauhmin, tauhdiff
}

UNITS	{
	(S) = (siemens)
	(mV) = (millivolt)
	(mA) = (milliamp)
}

PARAMETER	{
	gCa_LVAstbar = 0.00001 (S/cm2)
	offma = -40.0 (mV)
	offmt = -35.0 (mV)
	offha = -90.0 (mV)
	offht = -50.0 (mV)
	sloma = 6.0 (mV)
	slomt = 5.0 (mV)
	sloha = 6.4 (mV)
	sloht = 7.0 (mV)
	taummin = 5.0 (ms)
	taumdiff = 20.0 (ms)
	tauhmin = 20.0 (ms)
	tauhdiff = 50.0 (ms)
}

ASSIGNED	{
	v	(mV)
	eca	(mV)
	ica	(mA/cm2)
	gCa_LVAst	(S/cm2)
	mInf
	mTau
	hInf
	hTau
}

STATE	{
	m
	h
}

BREAKPOINT	{
	SOLVE states METHOD cnexp
	gCa_LVAst = gCa_LVAstbar*m*m*h
	ica = gCa_LVAst*(v-eca)
}

DERIVATIVE states	{
	rates()
	m' = (mInf-m)/mTau
	h' = (hInf-h)/hTau
}

INITIAL{
	rates()
	m = mInf
	h = hInf
}

PROCEDURE rates(){
  LOCAL qt
  qt = 2.3^((34-21)/10)

	UNITSOFF
		mInf = 1.0000/(1+ exp((offma-v)/sloma))
		mTau = (taummin + taumdiff/(1+exp(-(offmt-v)/slomt)))/qt
		hInf = 1.0000/(1+ exp(-(offha-v)/sloha))
		hTau = (tauhmin + tauhdiff/(1+exp(-(offht-v)/sloht)))/qt
	UNITSON
}

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