Early-onset epileptic encephalopathy (Miceli et al. 2015)

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Accession:170030
Model files from the paper "Early-Onset Epileptic Encephalopathy Caused by Gain-of-Function Mutations in the Voltage Sensor of Kv7.2 and Kv7.3 Potassium Channel Subunits" by Francesco Miceli, Maria Virginia Soldovieri, Paolo Ambrosino, Michela De Maria, Michele Migliore, Rosanna Migliore, and Maurizio Taglialatela J Neurosci. 2015 Mar 4;35(9):3782-93. The file fig7C.hoc reproduces the simulations shown in Fig.7C of the paper.
Reference:
1 . Miceli F, Soldovieri MV, Ambrosino P, De Maria M, Migliore M, Migliore R, Taglialatela M (2015) Early-onset epileptic encephalopathy caused by gain-of-function mutations in the voltage sensor of Kv7.2 and Kv7.3 potassium channel subunits. J Neurosci 35:3782-93 [PubMed]
Citations  Citation Browser
Model Information (Click on a link to find other models with that property)
Model Type: Dendrite;
Brain Region(s)/Organism: Hippocampus;
Cell Type(s): Hippocampus CA1 pyramidal cell;
Channel(s): I Na,t; I A; I K; I M; I h;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s): Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Epilepsy;
Implementer(s): Migliore, Michele [Michele.Migliore at Yale.edu];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal cell; I Na,t; I A; I K; I M; I h; Glutamate;
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Kv72_ModelDB
readme.html
h.mod *
kadist.mod *
kamt.mod *
kaprox.mod *
kdrca1.mod *
ks.mod *
kv72wt73wt.mod *
kv72wt73wtR201C.mod
na3n.mod *
naxn.mod *
netstims.mod *
fig7C.hoc
fixnseg.hoc *
geo5038804-S.hoc
mosinit.hoc
olm-t.hoc
screenshot1.png
screenshot2.png
                            
TITLE K-A channel from Klee Ficker and Heinemann
: modified to account for Dax A Current --- M.Migliore Jun 1997
: modified to be used with cvode  M.Migliore 2001

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

}

PARAMETER {
	v (mV)
	celsius		(degC)
	gkabar=.008 (mho/cm2)
        vhalfn=11   (mV)
        vhalfl=-56   (mV)
        a0l=0.05      (/ms)
        a0n=0.05    (/ms)
        zetan=-1.5    (1)
        zetal=3    (1)
        gmn=0.55   (1)
        gml=1   (1)
	lmin=2  (mS)
	nmin=0.1  (mS)
	pw=-1    (1)
	tq=-40
	qq=5
	q10=5
	qtl=1
	ek
}


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

STATE {
	n
        l
}

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

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


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

}


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

FUNCTION betn(v(mV)) {
LOCAL zeta
  zeta=zetan+pw/(1+exp((v-tq)/qq))
  betn = exp(1.e-3*zeta*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 {     : exact when v held constant; integrates over dt step
        rates(v)
        n' = (ninf - n)/taun
        l' =  (linf - l)/taul
}

PROCEDURE rates(v (mV)) { :callable from hoc
        LOCAL a,qt
        qt=q10^((celsius-24)/10)
        a = alpn(v)
        ninf = 1/(1 + a)
        taun = betn(v)/(qt*a0n*(1+a))
	if (taun<nmin) {taun=nmin}
        a = alpl(v)
        linf = 1/(1+ a)
	taul = 0.26*(v+50)/qtl
	if (taul<lmin/qtl) {taul=lmin/qtl}
}