CA1 pyramidal neuron: effects of R213Q and R312W Kv7.2 mutations (Miceli et al. 2013)

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Accession:148094
NEURON mod files from the paper: Miceli et al, Genotype–phenotype correlations in neonatal epilepsies caused by mutations in the voltage sensor of Kv7.2 potassium channel subunits, PNAS 2013 Feb 25. [Epub ahead of print] In this paper, functional studies revealed that in homomeric or heteromeric configuration with KV7.2 and/or KV7.3 subunits, R213W and R213Q mutations markedly destabilized the open state, causing a dramatic decrease in channel voltage sensitivity. Modeling these channels in CA1 hippocampal pyramidal cells revealed that both mutations increased cell firing frequency, with the R213Q mutation prompting more dramatic functional changes compared with the R213W mutation.
Reference:
1 . Miceli F, Soldovieri MV, Ambrosino P, Barrese V, Migliore M, Cilio MR, Taglialatela M (2013) Genotype-phenotype correlations in neonatal epilepsies caused by mutations in the voltage sensor of Kv7.2 potassium channel subunits. Proc Natl Acad Sci U S A 110(11):4386-91 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Channel/Receptor; 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 Calcium;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Active Dendrites; Action Potentials; 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 Calcium;
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kv72-R213QW-mutations
readme.html
cacumm.mod
cad.mod
cagk.mod *
cal2.mod *
cat.mod *
h.mod *
kadist.mod *
KahpM95.mod *
kaprox.mod *
kdrca1.mod *
kv72wt73wt.mod *
kv72wt73wt72R213Q.mod
kv72wt73wt72R213W.mod
na3n.mod *
naxn.mod *
fig4a.hoc
fixnseg.hoc *
geo9068802.hoc *
mosinit.hoc *
                            
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}
}















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