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 decay of internal calcium concentration
:
: Internal calcium concentration due to calcium currents and pump.
: Differential equations.
:
: Simple model of ATPase pump with 3 kinetic constants (Destexhe 92)
:     Cai + P <-> CaP -> Cao + P  (k1,k2,k3)
: A Michaelis-Menten approximation is assumed, which reduces the complexity
: of the system to 2 parameters: 
:       kt = <tot enzyme concentration> * k3  -> TIME CONSTANT OF THE PUMP
:	kd = k2/k1 (dissociation constant)    -> EQUILIBRIUM CALCIUM VALUE
: The values of these parameters are chosen assuming a high affinity of 
: the pump to calcium and a low transport capacity (cfr. Blaustein, 
: TINS, 11: 438, 1988, and references therein).  
:
: Units checked using "modlunit" -> factor 10000 needed in ca entry
:
: VERSION OF PUMP + DECAY (decay can be viewed as simplified buffering)
:
: All variables are range variables
:
: adopted from the lower model by AS 102199
:
: This mechanism was published in:  Destexhe, A. Babloyantz, A. and 
: Sejnowski, TJ.  Ionic mechanisms for intrinsic slow oscillations in
: thalamic relay neurons. Biophys. J. 65: 1538-1552, 1993)
:
: Written by Alain Destexhe, Salk Institute, Nov 12, 1992
:

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

NEURON {
	SUFFIX cad
	USEION ca READ ica, cai WRITE cai
	RANGE ca,depth,cainf,taur
}

UNITS {
	(molar) = (1/liter)			: moles do not appear in units
	(mM)	= (millimolar)
	(um)	= (micron)
	(mA)	= (milliamp)
	(msM)	= (ms mM)
	FARADAY = (faraday) (coulomb)
}


PARAMETER {
	depth	= .1	(um)		: depth of shell
	taur	= 80	(ms)		: rate of calcium removal, changed from 200 to 80 (H.Markram)
	cainf	= 100e-6(mM)
	cai		(mM)
	gamma = 1.0
}

STATE {
	ca		(mM) 
}

INITIAL {
	ca = cainf
}

ASSIGNED {
	ica		(mA/cm2)
	drive_channel	(mM/ms)
}
	
BREAKPOINT {
	SOLVE state METHOD cnexp
}

DERIVATIVE state { 

	drive_channel =  - (10000) * ica * gamma / (2 * FARADAY * depth)
	if (drive_channel <= 0.) { drive_channel = 0. }	: cannot pump inward

	ca' = drive_channel + (cainf-ca)/taur
	cai = ca
}