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 F, Pascotto A, Taglialatela M (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 34:501-10 [PubMed]
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 GLU 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 GLU 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 CA1 KM channel from M. Taglialatela
: M. Migliore Oct 2008

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

}

PARAMETER {
	v 		(mV)
	ek
	celsius 	(degC)
	gbar=.0001 	(mho/cm2)
        vhalfl=-32.4   	(mV)
	kl=-12.2
        vhalft=-60   	(mV)
        a0a=0.006      	(/ms)
        zetat=3    	(1)
        gmt=.62   	(1)
        vhalfb=-49   	(mV)
        a0b=0.0039      	(/ms)
        zetab=4.5    	(1)
        gmb=.4   	(1)
	q10=3.8
	b0=40
	b0b=25
}


NEURON {
	SUFFIX kmtwt
	USEION k READ ek WRITE ik
        RANGE  gbar,ik
      GLOBAL inf, tau, taua, taub
}

STATE {
        m
}

ASSIGNED {
	ik (mA/cm2)
        inf
	tau
        taua
	taub
}

INITIAL {
	rate(v)
	m=inf
}


BREAKPOINT {
	SOLVE state METHOD cnexp
	ik = gbar*m*(v-ek)
}


FUNCTION alpa(v(mV)) {
  alpa = exp(0.0378*zetat*(v-vhalft)) 
}

FUNCTION alpb(v(mV)) {
  alpb = exp(0.0378*zetab*(v-vhalfb)) 
}


FUNCTION beta(v(mV)) {
  beta = exp(0.0378*zetat*gmt*(v-vhalft)) 
}

FUNCTION betb(v(mV)) {
  betb = exp(0.0378*zetab*gmb*(v-vhalfb)) 
}

DERIVATIVE state {
        rate(v)
        if (m<inf) {tau=taua} else {tau=taub}
	m' = (inf - m)/tau
}

PROCEDURE rate(v (mV)) { :callable from hoc
        LOCAL a,qt, ab
        qt=q10^((celsius-22)/10)
        inf = (1/(1 + exp((v-vhalfl)/kl)))
        a = alpa(v)
        ab = alpb(v)
        taua = (b0 + beta(v)/(a0a*(1+a)))/qt
        taub = (b0b + betb(v)/(a0b*(1+ab)))/qt
}















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