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]
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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 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 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 Borg-Graham type generic K-A channel
UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)

}

PARAMETER {
	v (mV)
        ek (mV)
	celsius 	(degC)
	gkabar=.01 (mho/cm2)
        vhalfn=-33.6   (mV)
        vhalfl=-83   (mV)
        a0l=0.08      (/ms)
        a0n=0.02    (/ms)
        zetan=-3    (1)
        zetal=4    (1)
        gmn=0.6   (1)
        gml=1   (1)
}


NEURON {
	SUFFIX borgka
	USEION k READ ek WRITE ik
        RANGE gkabar,gka, ik
        GLOBAL ninf,linf,taul,taun
}

STATE {
	n
        l
}

INITIAL {
        rates(v)
        n=ninf
        l=linf
}

ASSIGNED {
	ik (mA/cm2)
        ninf
        linf      
        taul
        taun
        gka
}

BREAKPOINT {
	SOLVE states METHOD cnexp
	gka = gkabar*n*l
	ik = gka*(v-ek)

}


FUNCTION alpn(v(mV)) {
  alpn = exp(1.e-3*zetan*(v-vhalfn)*9.648e4/(8.315*(273.16+celsius))) 
}

FUNCTION betn(v(mV)) {
  betn = exp(1.e-3*zetan*gmn*(v-vhalfn)*9.648e4/(8.315*(273.16+celsius))) 
}

FUNCTION alpl(v(mV)) {
  alpl = exp(1.e-3*zetal*(v-vhalfl)*9.648e4/(8.315*(273.16+celsius))) 
}

FUNCTION betl(v(mV)) {
  betl = exp(1.e-3*zetal*gml*(v-vhalfl)*9.648e4/(8.315*(273.16+celsius))) 
}

DERIVATIVE states { 
        rates(v)
        n' = (ninf - n)/taun
        l' = (linf - l)/taul
}

PROCEDURE rates(v (mV)) { :callable from hoc
        LOCAL a,q10
        q10=3^((celsius-30)/10)
        a = alpn(v)
        ninf = 1/(1 + a)
        taun = betn(v)/(q10*a0n*(1+a))
        a = alpl(v)
        linf = 1/(1+ a)
        taul = betl(v)/(q10*a0l*(1 + a))
}