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 I-h channel from Magee 1998 for distal dendrites

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

}

PARAMETER {
	v 		(mV)
        ehd  		(mV)        
	celsius 	(degC)
	ghdbar=.0001 	(mho/cm2)
        vhalfl=-73   	(mV)
	kl=-8
        vhalft=-75   	(mV)
        a0t=0.011      	(/ms)
        zetat=2.2    	(1)
        gmt=.4   	(1)
	q10=4.5
	qtl=1
}


NEURON {
	SUFFIX hd
	NONSPECIFIC_CURRENT i
        RANGE ghdbar, vhalfl
        GLOBAL linf,taul
}

STATE {
        l
}

ASSIGNED {
	i (mA/cm2)
        linf      
        taul
        ghd
}

INITIAL {
	rate(v)
	l=linf
}


BREAKPOINT {
	SOLVE states METHOD cnexp
	ghd = ghdbar*l
	i = ghd*(v-ehd)

}


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

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

DERIVATIVE states {     : exact when v held constant; integrates over dt step
        rate(v)
        l' =  (linf - l)/taul
}

PROCEDURE rate(v (mV)) { :callable from hoc
        LOCAL a,qt
        qt=q10^((celsius-33)/10)
        a = alpt(v)
        linf = 1/(1 + exp(-(v-vhalfl)/kl))
:       linf = 1/(1+ alpl(v))
        taul = bett(v)/(qtl*qt*a0t*(1+a))
}















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