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
AdultD82GRed
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

kca.mod

Calcium-dependent potassium channel
Based on
Pennefather (1990) -- sympathetic ganglion cells
taken from
Reuveni et al (1993) -- neocortical cells

Author: Zach Mainen, Salk Institute, 1995, zach@salk.edu

Kole: the caix increased from 1 -> 4, Ra 0.01 to 0.05 and Rb 0.02 to 0.1, according to Schaefer et al, 2003 to allow BAC firing
	
ENDCOMMENT

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

NEURON {
	SUFFIX kca
	USEION k READ ek WRITE ik
	USEION ca READ cai
	RANGE n, gkca, ikca, gbar
	RANGE ninf, ntau
	GLOBAL Ra, Rb, caix
	GLOBAL q10, temp, tadj, vmin, vmax
}

UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)
	(pS) = (picosiemens)
	(um) = (micron)
} 

PARAMETER {
	gbar = 10   	(pS/um2)	: 0.03 mho/cm2
	v 		(mV)
	cai  		(mM)
	caix = 4	
									
	Ra   = 0.05	(/ms)		: max act rate  
	Rb   = 0.1	(/ms)		: max deact rate 

	dt		(ms)
	celsius		(degC)
	temp = 23	(degC)		: original temp 	
	q10  = 2.3			: temperature sensitivity

	vmin = -120	(mV)
	vmax = 100	(mV)
} 


ASSIGNED {
	a		(/ms)
	b		(/ms)
	ik 		(mA/cm2)
	ikca 		(mA/cm2)
	gkca		(pS/um2)
	ek		(mV)
	ninf
	ntau 		(ms)	
	tadj
}
 

STATE { n }

INITIAL { 
	rates(cai)
	n = ninf
}

BREAKPOINT {
        SOLVE states METHOD cnexp
	gkca =gbar*n
	ikca = (1e-4) * gkca * (v - ek)
	ik = ikca
} 

LOCAL nexp

DERIVATIVE states {   :Computes state variable n 
        rates(cai)      :             at the current v and dt.
        n' =  (ninf-n)/ntau

}

PROCEDURE rates(cai(mM)) {  

        

        a = Ra * cai^caix
        b = Rb

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

        ntau = 1/tadj/(a+b)
	ninf = a/(a+b)

 
:        tinc = -dt * tadj
:        nexp = 1 - exp(tinc/ntau)
}













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