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]
Citations  Citation Browser
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
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COMMENT
	calcium accumulation into a volume of area*depth next to the
	membrane with a decay (time constant tau) to resting level
	given by the global calcium variable cai0_ca_ion
	Modified to include a resting current (irest) and peak value
	(cmax)
	i is a dummy current needed to force a BREAKPOINT
ENDCOMMENT

NEURON {
	SUFFIX cacum
	USEION ca READ ica WRITE cai
	NONSPECIFIC_CURRENT i
	RANGE depth, tau, cai0, cmax
}

UNITS {
	(mM) = (milli/liter)
	(mA) = (milliamp)
	F = (faraday) (coulombs)
}

PARAMETER {
	depth = 0.1 (um)	: assume volume = area*depth
	irest = 0  (mA/cm2)		: to be initialized in hoc	
	tau = 100 (ms)
	cai0 = 50e-6 (mM)	: Requires explicit use in INITIAL
			: block for it to take precedence over cai0_ca_ion
			: Do not forget to initialize in hoc if different
			: from this default.
}

ASSIGNED {
	ica (mA/cm2)
	cmax
	i  	 (mA/cm2)
}

STATE {
	cai (mM)
}

INITIAL {
	cai = cai0
	irest = ica
	cmax=cai
}

BREAKPOINT {
	SOLVE integrate METHOD derivimplicit
	if (cai>cmax) {cmax=cai}
	i=0
}

DERIVATIVE integrate {
	cai' = (irest-ica)/depth/F/2 * (1e4) + (cai0 - cai)/tau
}