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
AdultT1420MRed
readme.txt *
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 *
28_04_10_num19.hoc *
all_28_04_10_num19.ses *
Cell parameters.hoc *
charge.hoc *
mosinit.hoc *
scn2aExps.hoc
                            
COMMENT

changed from (AS Oct0899)
ca.mod to lead to thalamic ca current inspired by destexhe and huguenrd
Uses fixed eca instead of GHK eqn

ENDCOMMENT

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

NEURON {
	SUFFIX it2
	USEION ca READ eca WRITE ica
	RANGE m, h, gcaT, icaT, gcabar
	RANGE minf, hinf, mtau, htau, inactF, actF
	GLOBAL  vshift,vmin,vmax, v12m, v12h, vwm, vwh, am, ah, vm1, vm2, vh1, vh2, wm1, wm2, wh1, wh2
}

PARAMETER {
	gcabar = 8 	(pS/um2)	: 0.12 mho/cm2
	vshift = 0	(mV)		: voltage shift (affects all)

	cao  = 2.0	(mM)	        : external ca concentration
	cai		(mM)
						 
	v 		(mV)
	dt		(ms)
	celsius		(degC)
	vmin = -120	(mV)
	vmax = 100	(mV)

	v12m=50         	(mV)
	v12h=78         	(mV)
	vwm =7.4         	(mV)
	vwh=5.0         	(mV)
	am=3         	(mV)
	ah=85         	(mV)
	vm1=25         	(mV)
	vm2=100         	(mV)
	vh1=46         	(mV)
	vh2=405         	(mV)
	wm1=20         	(mV)
	wm2=15         	(mV)
	wh1=4         	(mV)
	wh2=50         	(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)
	icaT 		(mA/cm2)
	gcaT		(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
        gcaT = gcabar*m*m*h
	icaT = gcaT *(1e-4)* (v - eca)
	ica = icaT
} 

LOCAL mexp, hexp

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


PROCEDURE trates(v) {  
                      
        LOCAL tinc
        TABLE minf, mexp, hinf, hexp
	DEPEND dt	
	FROM vmin TO vmax WITH 199

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

        tinc = -dt 

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


PROCEDURE rates(v_) {  
        LOCAL  a, b

	minf = 1.0 / ( 1 + exp(-(v_+v12m)/vwm) )
	hinf = 1.0 / ( 1 + exp((v_+v12h)/vwh) )

	mtau = ( am + 1.0 / ( exp((v_+vm1)/wm1) + exp(-(v_+vm2)/wm2) ) ) 
	htau = ( ah + 1.0 / ( exp((v_+vh1)/wh1) + exp(-(v_+vh2)/wh2) ) ) 
}


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