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 gskch.mod  calcium-activated potassium channel (non-voltage-dependent)

COMMENT

gsk granule

ENDCOMMENT

UNITS {
        (molar) = (1/liter)
        (mM)    = (millimolar)
	(mA)	= (milliamp)
	(mV)	= (millivolt)
}

NEURON {
	SUFFIX gskch
	USEION sk READ esk WRITE isk VALENCE 1
	USEION nca READ ncai VALENCE 2
	USEION lca READ lcai VALENCE 2
	USEION tca READ tcai VALENCE 2
	RANGE gsk, gskbar, qinf, qtau, isk
}

INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}

PARAMETER {
	celsius=6.3 (degC)
	v		(mV)
	dt		(ms)
	gskbar  (mho/cm2)
	esk	(mV)
	cai (mM)
	ncai (mM)
	lcai (mM)
	tcai (mM)
}

STATE { q }

ASSIGNED {
	isk (mA/cm2) gsk (mho/cm2) qinf qtau (ms) qexp
}


BREAKPOINT {          :Computes i=g*q^2*(v-esk)
	SOLVE state
        gsk = gskbar * q*q
	isk = gsk * (v-esk)
}

UNITSOFF

INITIAL {
	cai = ncai + lcai + tcai	
	q=qinf
	rate(cai)
	VERBATIM
	ncai = _ion_ncai;
	lcai = _ion_lcai;
	tcai = _ion_tcai;
	ENDVERBATIM
}


PROCEDURE state() {  :Computes state variable q at current v and dt.
	cai = ncai + lcai + tcai
	rate(cai)
	q = q + (qinf-q) * qexp
	VERBATIM
	return 0;
	ENDVERBATIM
}

LOCAL q10
PROCEDURE rate(cai) {  :Computes rate and other constants at current v.
	LOCAL alpha, beta, tinc
	q10 = 3^((celsius - 6.3)/10)
		:"q" activation system
alpha = 1.25e1 * cai * cai
beta = 0.00025 

:	alpha = 0.00246/exp((12*log10(cai)+28.48)/-4.5)
:	beta = 0.006/exp((12*log10(cai)+60.4)/35)
: alpha = 0.00246/fctrap(cai)
: beta = 0.006/fctrap(cai)
	qtau = 1 / (alpha + beta)
	qinf = alpha * qtau
	tinc = -dt*q10
	qexp = 1 - exp(tinc/qtau)*q10
}

UNITSON

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