Pyramidal neurons with mutated SCN2A gene (Nav1.2) (Ben-Shalom et al 2017)

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Accession:223955
Model of pyramidal neurons that either hyper or hypo excitable due to SCN2A mutations. Mutations are taken from patients with ASD or Epilepsy
Reference:
1 . Ben-Shalom R, Keeshen CM,Berrios KN, An JY, Sanders SJ, Bender KJ (2017) Opposing effects on NaV1.2 function underlie differences between SCN2A variants observed in individuals with autism spectrum disorder or infantile seizures Biological Psychiatry, epub before print
Model Information (Click on a link to find other models with that property)
Model Type:
Brain Region(s)/Organism:
Cell Type(s): Neocortex V1 pyramidal corticothalamic L6 cell;
Channel(s): I Na,t; I Sodium; I K;
Gap Junctions:
Receptor(s):
Gene(s): Nav1.2 SCN2A;
Transmitter(s):
Simulation Environment: NEURON; MATLAB;
Model Concept(s):
Implementer(s): Ben-Shalom, Roy [bens.roy at gmail.com];
Search NeuronDB for information about:  Neocortex V1 pyramidal corticothalamic L6 cell; I Na,t; I K; I Sodium;
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SCN2A_ASD
Excitability
YoungD82G
Cad.mod *
CaH.mod *
CaT.mod *
charge.mod *
h.mod *
Kca.mod *
Kv.mod *
Kv1_axonal.mod *
Kv7.mod *
na8st.mod *
na8st1.mod *
nax8st.mod *
nax8st1.mod *
28_04_10_num19.hoc *
Cell parameters.hoc *
charge.hoc *
mosinit.hoc *
scn2aExps.hoc *
                            
COMMENT

ca.mod
Uses fixed eca instead of GHK eqn

HVA Ca current
Based on Reuveni, Friedman, Amitai and Gutnick (1993) J. Neurosci. 13:
4609-4621.

Author: Zach Mainen, Salk Institute, 1994, zach@salk.edu

ENDCOMMENT

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

NEURON {
	SUFFIX ca
	USEION ca READ eca WRITE ica
	RANGE m, h, gcaH, icaH, gbar
	RANGE minf, hinf, mtau, htau
	GLOBAL q10, temp, tadj, vmin, vmax, vshift
}

PARAMETER {
	gbar = 0.1   	(pS/um2)	: 0.12 mho/cm2
	vshift = 0	(mV)		: voltage shift (affects all)

	cao  = 2.0	(mM)	        : external ca concentration
	cai		(mM)
						
	temp = 23	(degC)		: original temp 
	q10  = 2.3			: temperature sensitivity

	v 		(mV)
	dt		(ms)
	celsius		(degC)
	vmin = -120	(mV)
	vmax = 100	(mV)
}


UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)
	(pS) = (picosiemens)
	(um) = (micron)
	FARADAY = (faraday) (coulomb)
	R = (k-mole) (joule/degC)
	PI	= (pi) (1)
} 

ASSIGNED {
	ica 		(mA/cm2)
	icaH 		(mA/cm2)
	gcaH		(pS/um2)
	eca		(mV)
	minf 		hinf
	mtau (ms)	htau (ms)
	tadj
}
 

STATE { m h }

INITIAL { 
	trates(v+vshift)
	m = minf
	h = hinf
}

BREAKPOINT {
        SOLVE states METHOD cnexp
        gcaH = gbar*m*m*h
	icaH = (1e-4) * gcaH * (v - eca)
	ica = icaH
} 

LOCAL mexp, hexp

:PROCEDURE states() {
:        trates(v+vshift)      
:        m = m + mexp*(minf-m)
:        h = h + hexp*(hinf-h)
:	VERBATIM
:	return 0;
:	ENDVERBATIM
:}

DERIVATIVE states {
        trates(v+vshift)      
        m' =  (minf-m)/mtau
        h' =  (hinf-h)/htau
}

PROCEDURE trates(v) {  
                      
        
        TABLE minf, hinf, mtau, htau 
	DEPEND  celsius, temp
	
	FROM vmin TO vmax WITH 199

	rates(v): not consistently executed from here if usetable == 1

:        tinc = -dt * tadj

:        mexp = 1 - exp(tinc/mtau)
:        hexp = 1 - exp(tinc/htau)
}


PROCEDURE rates(vm) {  
        LOCAL  a, b

        tadj = q10^((celsius - temp)/10)

	a = 0.055*(-27 - vm)/(exp((-27-vm)/3.8) - 1)
	b = 0.94*exp((-75-vm)/17)
	
	mtau = 1/tadj/(a+b)
	minf = a/(a+b)

		:"h" inactivation 

	a = 0.000457*exp((-13-vm)/50)
	b = 0.0065/(exp((-vm-15)/28) + 1)

	htau = 1/tadj/(a+b)
	hinf = a/(a+b)
}

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


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