State dependent drug binding to sodium channels in the dentate gyrus (Thomas & Petrou 2013)

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Accession:149174
A Markov model of sodium channels was developed that includes drug binding to fast inactivated states. This was incorporated into a model of the dentate gyrus to investigate the effects of anti-epileptic drugs on neuron and network properties.
Reference:
1 . Thomas EA, Petrou S (2013) Network-specific mechanisms may explain the paradoxical effects of carbamazepine and phenytoin. Epilepsia 54:1195-202 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network; Neuron or other electrically excitable cell; Axon; Channel/Receptor;
Brain Region(s)/Organism:
Cell Type(s): Dentate gyrus granule GLU cell; Dentate gyrus mossy cell; Dentate gyrus basket cell; Dentate gyrus hilar cell;
Channel(s): I Na,t; I A; I_AHP;
Gap Junctions:
Receptor(s): GabaA; AMPA;
Gene(s):
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON; MATLAB;
Model Concept(s): Ion Channel Kinetics; Epilepsy; Calcium dynamics; Drug binding; Markov-type model;
Implementer(s): Thomas, Evan [evan at evan-thomas.net];
Search NeuronDB for information about:  Dentate gyrus granule GLU cell; GabaA; AMPA; I Na,t; I A; I_AHP; Gaba; Glutamate;
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ThomasPetrou2013
Fig 4
Data
bgka.mod *
CaBK.mod *
ccanl.mod *
Gfluct2.mod *
gskch.mod *
hyperde3.mod *
ichan2.mod
LcaMig.mod *
nad.mod
nca.mod *
tca.mod *
apchew.m
async.hoc
runall.py
                            
TITLE T-calcium channel From Migliore CA3
: T-type calcium channel


UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)

	FARADAY = 96520 (coul)
	R = 8.3134 (joule/degC)
	KTOMV = .0853 (mV/degC)
}

PARAMETER {
	v (mV)
	celsius = 6.3	(degC)
	gcatbar=.003 (mho/cm2)
	cai (mM)
	cao (mM)
}


NEURON {
	SUFFIX cat
	USEION tca READ etca WRITE itca VALENCE 2
	USEION ca READ cai, cao VALENCE 2
        RANGE gcatbar,cai, itca, etca
}

STATE {
	m h 
}

ASSIGNED {
	itca (mA/cm2)
        gcat (mho/cm2)
	etca (mV)
}

INITIAL {
      m = minf(v)
      h = hinf(v)
	VERBATIM
	cai=_ion_cai;
	ENDVERBATIM
}

BREAKPOINT {
	SOLVE states METHOD cnexp
	gcat = gcatbar*m*m*h
	itca = gcat*ghk(v,cai,cao)

}

DERIVATIVE states {	: exact when v held constant
	m' = (minf(v) - m)/m_tau(v)
	h' = (hinf(v) - h)/h_tau(v)
}


FUNCTION ghk(v(mV), ci(mM), co(mM)) (mV) {
        LOCAL nu,f

        f = KTF(celsius)/2
        nu = v/f
        ghk=-f*(1. - (ci/co)*exp(nu))*efun(nu)
}

FUNCTION KTF(celsius (DegC)) (mV) {
        KTF = ((25./293.15)*(celsius + 273.15))
}


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

FUNCTION hinf(v(mV)) {
	LOCAL a,b
	TABLE FROM -150 TO 150 WITH 200
	a = 1.e-6*exp(-v/16.26)
	b = 1/(exp((-v+29.79)/10)+1)
	hinf = a/(a+b)
}

FUNCTION minf(v(mV)) {
	LOCAL a,b
	TABLE FROM -150 TO 150 WITH 200
        
	a = 0.2*(-1.0*v+19.26)/(exp((-1.0*v+19.26)/10.0)-1.0)
	b = 0.009*exp(-v/22.03)
	minf = a/(a+b)
}

FUNCTION m_tau(v(mV)) (ms) {
	LOCAL a,b
	TABLE FROM -150 TO 150 WITH 200
	a = 0.2*(-1.0*v+19.26)/(exp((-1.0*v+19.26)/10.0)-1.0)
	b = 0.009*exp(-v/22.03)
	m_tau = 1/(a+b)
}

FUNCTION h_tau(v(mV)) (ms) {
	LOCAL a,b
        TABLE FROM -150 TO 150 WITH 200
	a = 1.e-6*exp(-v/16.26)
	b = 1/(exp((-v+29.79)/10.)+1.)
	h_tau = 1/(a+b)
}

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