CA1 pyramidal neurons: effects of a Kv7.2 mutation (Miceli et al. 2009)

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Accession:118986
NEURON mod files from the paper: Miceli et al, Neutralization of a unique, negatively-charged residue in the voltage sensor of K(V)7.2 subunits in a sporadic case of benign familial neonatal seizures, Neurobiol Dis., in press (2009). In this paper, the model revealed that the gating changes introduced by a mutation in K(v)7.2 genes encoding for the neuronal KM current in a case of benign familial neonatal seizures, increased cell firing frequency, thereby triggering the neuronal hyperexcitability which underlies the observed neonatal epileptic condition.
Reference:
1 . Miceli F, Soldovieri MV, Lugli L, Bellini G, Ambrosino P, Migliore M, Del Giudice EM, Ferrari (2009) Neutralization of a unique, negatively-charged residue in the voltage sensor of K(V)7.2 subunits in a sporadic case of benign familial neonatal seizures. Neurobiol Dis [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 T low threshold; I A; I K; I M; I h;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Activity Patterns; Ion Channel Kinetics; Active Dendrites; Detailed Neuronal Models; Action Potentials;
Implementer(s): Migliore, Michele [Michele.Migliore at Yale.edu];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal cell; I Na,t; I T low threshold; I A; I K; I M; I h;
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mutant
readme.html
cacumm.mod *
cat.mod *
h.mod *
kadist.mod *
KahpM95.mod *
kaprox.mod *
kdrca1.mod *
kmquad.mod
kmtwt.mod
na3n.mod *
naxn.mod *
fig6a.hoc
fixnseg.hoc *
geo9068802.hoc *
mosinit.hoc
screenshot.jpg
                            
TITLE K-DR channel
: from Klee Ficker and Heinemann
: modified to account for Dax et al.
: M.Migliore 1997

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

}

PARAMETER {
	v (mV)
        ek (mV)		: must be explicitely def. in hoc
	celsius		(degC)
	gkdrbar=.003 (mho/cm2)
        vhalfn=13   (mV)
        a0n=0.02      (/ms)
        zetan=-3    (1)
        gmn=0.7  (1)
	nmax=2  (1)
	q10=1
}


NEURON {
	SUFFIX kdr
	USEION k READ ek WRITE ik
        RANGE gkdr,gkdrbar
	GLOBAL ninf,taun
}

STATE {
	n
}

ASSIGNED {
	ik (mA/cm2)
        ninf
        gkdr
        taun
}

BREAKPOINT {
	SOLVE states METHOD cnexp
	gkdr = gkdrbar*n
	ik = gkdr*(v-ek)

}

INITIAL {
	rates(v)
	n=ninf
}


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))) 
}

DERIVATIVE states {     : exact when v held constant; integrates over dt step
        rates(v)
        n' = (ninf - n)/taun
}

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<nmax) {taun=nmax}
}