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

 Download zip file   Auto-launch 
Help downloading and running models
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]
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;
/
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-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}
}















Loading data, please wait...