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
                            
COMMENT
	calcium accumulation into a volume of area*depth next to the
	membrane with a decay (time constant tau) to resting level
	given by the global calcium variable cai0_ca_ion
ENDCOMMENT

NEURON {
	SUFFIX ccanl
USEION nca READ ncai, inca, enca WRITE enca, ncai VALENCE 2
USEION lca READ lcai, ilca, elca WRITE elca, lcai VALENCE 2
USEION tca READ tcai, itca, etca WRITE etca, tcai VALENCE 2
RANGE caiinf, catau, cai, ncai, lcai,tcai, eca, elca, enca, etca
}

UNITS {
        (mV) = (millivolt)
	(molar) = (1/liter)
	(mM) = (milli/liter)
	(mA) = (milliamp)
	FARADAY = 96520 (coul)
	R = 8.3134	(joule/degC)
}

INDEPENDENT {t FROM 0 TO 100 WITH 100 (ms)}

PARAMETER {
        celsius = 6.3 (degC)
	depth = 200 (nm)	: assume volume = area*depth
	catau = 9 (ms)
	caiinf = 50.e-6 (mM)	: takes precedence over cai0_ca_ion
			: Do not forget to initialize in hoc if different
			: from this default.
	cao = 2 (mM)
	ica (mA/cm2)
	inca (mA/cm2)
	ilca (mA/cm2)
	itca (mA/cm2)
	cai= 50.e-6 (mM)
}

ASSIGNED {
	enca (mV)
	elca (mV)
	etca (mV)
	eca (mV)
}

STATE {
	ncai (mM)
	lcai (mM)
	tcai (mM)
}

INITIAL {
	VERBATIM
	ncai = _ion_ncai;
	lcai = _ion_lcai;
	tcai = _ion_tcai; 
	ENDVERBATIM
	ncai=caiinf/3
	lcai=caiinf/3
	tcai=caiinf/3
	cai = caiinf	
	eca = ktf() * log(cao/caiinf)	
	enca = eca
	elca = eca
	etca = eca
}


BREAKPOINT {
	SOLVE integrate METHOD derivimplicit
	cai = ncai+lcai+tcai	
	eca = ktf() * log(cao/cai)	
	enca = eca
	elca = eca
	etca = eca
}

DERIVATIVE integrate {
ncai' = -(inca)/depth/FARADAY * (1e7) + (caiinf/3 - ncai)/catau
lcai' = -(ilca)/depth/FARADAY * (1e7) + (caiinf/3 - lcai)/catau
tcai' = -(itca)/depth/FARADAY * (1e7) + (caiinf/3 - tcai)/catau
}

FUNCTION ktf() (mV) {
	ktf = (1000)*R*(celsius +273.15)/(2*FARADAY)
}