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 CaGk
: Calcium activated K channel.
: Modified from Moczydlowski and Latorre (1983) J. Gen. Physiol. 82

UNITS {
	(molar) = (1/liter)
}

UNITS {
	(mV) =	(millivolt)
	(mA) =	(milliamp)
	(mM) =	(millimolar)
}


NEURON {
	SUFFIX cagk
	USEION nca READ ncai VALENCE 2
	USEION lca READ lcai VALENCE 2
	USEION tca READ tcai VALENCE 2
	USEION k READ ek WRITE ik
	RANGE gkbar,gkca, ik
	GLOBAL oinf, otau
}

UNITS {
	FARADAY = (faraday)  (kilocoulombs)
	R = 8.313424 (joule/degC)
}

PARAMETER {
	celsius		(degC)
	v		(mV)
	gkbar=.01	(mho/cm2)	: Maximum Permeability
	cai = 5.e-5	(mM)
	ek		(mV)

	d1 = .84
	d2 = 1.
	k1 = .48e-3	(mM)
	k2 = .13e-6	(mM)
	abar = .28	(/ms)
	bbar = .48	(/ms)
        st=1            (1)
	lcai		(mV)
	ncai		(mV)
	tcai		(mV)
}

ASSIGNED {
	ik		(mA/cm2)
	oinf
	otau		(ms)
        gkca          (mho/cm2)
}

INITIAL {
	cai= ncai + lcai + tcai
        rate(v,cai)
        o=oinf
}

STATE {	o }		: fraction of open channels

BREAKPOINT {
	SOLVE state METHOD cnexp
	gkca = gkbar*o^st
	ik = gkca*(v - ek)
}

DERIVATIVE state {	: exact when v held constant; integrates over dt step
	rate(v, cai)
	o' = (oinf - o)/otau
}

FUNCTION alp(v (mV), c (mM)) (1/ms) { :callable from hoc
	alp = c*abar/(c + exp1(k1,d1,v))
}

FUNCTION bet(v (mV), c (mM)) (1/ms) { :callable from hoc
	bet = bbar/(1 + c/exp1(k2,d2,v))
}

FUNCTION exp1(k (mM), d, v (mV)) (mM) { :callable from hoc
	exp1 = k*exp(-2*d*FARADAY*v/R/(273.15 + celsius))
}

PROCEDURE rate(v (mV), c (mM)) { :callable from hoc
	LOCAL a
	a = alp(v,c)
	otau = 1/(a + bet(v, c))
	oinf = a*otau
}