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
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geo9068802.hoc *
mosinit.hoc
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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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