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
YoungOrig
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
                            
TITLE Axonal voltage-gated potassium current

COMMENT
	Hallermann, de Kock, Stuart and Kole, Nature Neuroscience, 2012
	doi:10.1038/nn.3132
	
	n8*h1 + n8*h2 Hodgkin-Huxley model
ENDCOMMENT


NEURON {
	SUFFIX Kv1
	USEION k READ ek WRITE ik
	RANGE gkv1, ikv1, gbar
	GLOBAL ninf, ntau
	GLOBAL h1inf, h1tau
	GLOBAL h2inf, h2tau
	GLOBAL h3inf, h3tau
}

UNITS {
	(mV) = (millivolt)
	(mA) = (milliamp)
	(nA) = (nanoamp)
	(pA) = (picoamp)
	(S)  = (siemens)
	(nS) = (nanosiemens)
	(pS) = (picosiemens)
	(um) = (micron)
	(molar) = (1/liter)
	(mM) = (millimolar)		
}


CONSTANT {
:	ek = -98 (mV)
	a1 = 48.02279
	a2 = 42.662
	b1 = 58.44509
	c1 = 13.44182
	c2 = 49.38797

	a1H1 = 1.300293e-03
	a2H1 = 6.247311
	b2H1 = 66.13843
	c1H1 = 8.611435
	c2H1 = 7.948768

	a12H2fact = 1.554639e-02
	propH2 = 0.73157
	sToMs = 0.001
}


PARAMETER {
	v (mV)

	vShift = 0
	vShift_inact = 0
	gbar (pS/um2)
	temp = 33	(degC)		: original temp 
	q10  = 3			: temperature sensitivity
	q10h  = 3			: temperature sensitivity for inactivation
	celsius		(degC)
}


ASSIGNED {
 	ik (mA/cm2) 
 	ikv1 (mA/cm2) 
	gkv1  (mho/cm2)
	ek (mV)

	ninf
	ntau (ms)
	nalpha (1/ms)
	nbeta (1/ms)

	h1inf
	h1tau (ms)
	h1alpha (1/ms)
	h1beta (1/ms)

	h2inf
	h2tau (ms)
	h2alpha (1/ms)
	h2beta (1/ms)

	h3inf
	h3tau (ms)
	h3alpha (1/ms)
	h3beta (1/ms)

	tadj
	tadjh
}

STATE { 
	n
	h1
	h2
}

INITIAL {
	rates(v)
	n = ninf
	h1 = h1inf
	h2 = h2inf
}

BREAKPOINT {
	SOLVE states METHOD cnexp
      	gkv1 = gbar * ( (1-propH2)*n^8*h1 + propH2*n^8*h2 )
	ikv1 = (1e-4)*gkv1 * (v - ek)
	ik = ikv1
}

DERIVATIVE states {
	rates(v)
	n' = (ninf-n)/ntau
	h1' = (h1inf-h1)/h1tau 
	h2' = (h2inf-h2)/h2tau 
}

PROCEDURE rates(v (mV)) {

	tadj = q10^((celsius - temp)/10)
	tadjh = q10h^((celsius - temp)/10)

	nalpha = tadj*nalphafkt(v-vShift)
	nbeta = tadj*nbetafkt(v-vShift)
	ninf = nalpha/(nalpha+nbeta) 
	ntau = 1/(nalpha + nbeta)

	h1alpha = tadjh*h1alphafkt(v-vShift-vShift_inact)
	h1beta = tadjh*h1betafkt(v-vShift-vShift_inact)
	h1inf = h1alpha/(h1alpha+h1beta) 
	h1tau = 1/(h1alpha + h1beta)

	h2alpha = tadjh*h2alphafkt(v-vShift-vShift_inact)
	h2beta = tadjh*h2betafkt(v-vShift-vShift_inact)
	h2inf = h2alpha/(h2alpha+h2beta) 
	h2tau = 1/(h2alpha + h2beta)
}

FUNCTION nalphafkt(v (mV)) (1/ms) {
	nalphafkt = sToMs * a1*(-(v+b1))/( exp(-(v+b1)/c1) -1)
}

FUNCTION nbetafkt(v (mV)) (1/ms) {
	nbetafkt = sToMs * a2*exp(-(v)/c2)
}

FUNCTION h1alphafkt(v (mV)) (1/ms) {
	h1alphafkt = sToMs * a1H1*exp(-(v)/c1H1)
}

FUNCTION h1betafkt(v (mV)) (1/ms) {
	h1betafkt = sToMs * a2H1/(exp(-(v+b2H1)/c2H1)+1)
}

FUNCTION h2alphafkt(v (mV)) (1/ms) {
	h2alphafkt = sToMs * a12H2fact*a1H1*exp(-(v)/c1H1)
}

FUNCTION h2betafkt(v (mV)) (1/ms) {
	h2betafkt = sToMs * a12H2fact*a2H1/(exp(-(v+b2H1)/c2H1)+1)
}

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