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 *
                            
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
:
:
: 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
	GLOBAL 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	= 200	(ms)		: rate of calcium removal
	cainf	= 100e-6(mM)
	cai		(mM)
}

STATE {
	ca		(mM) <1e-5>
}

INITIAL {
	ca = cainf
	cai = ca
}

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

DERIVATIVE state { 

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

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









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