Neurophysiological impact of inactivation pathways in A-type K+ channels (Fineberg et al 2012)

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Accession:145672
These models predict the differential effects of varying pathways of inactivation (closed state inactivation, CSI, or open state inactivation, OSI). Specifically, Markov models of Kv4 potassium channels with CSI or CSI+OSI were inserted into the CA1 pyramidal neuron model from Migliore et al (1999; ModelDB accession #2796) to determine the neurophysiological impact of inactivation pathways. Furthermore, Markov models of Kv4.2 and Kv3.4 channels are used to illustrate a method by which to test what pathway of inactivation a channel uses.
Reference:
1 . Fineberg JD, Ritter DM, Covarrubias M (2012) Modeling-independent elucidation of inactivation pathways in recombinant and native A-type Kv channels J Gen Physiol 140:513-527 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Channel/Receptor;
Brain Region(s)/Organism:
Cell Type(s): Hippocampus CA1 pyramidal cell;
Channel(s): I Na,t; I A; I K;
Gap Junctions:
Receptor(s):
Gene(s): Kv4.2 KCND2; Kv3.4 KCNC4;
Transmitter(s):
Simulation Environment: NEURON; IonChannelLab;
Model Concept(s): Ion Channel Kinetics; Markov-type model;
Implementer(s): Ritter, David [david.ritter at jefferson.edu];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal cell; I Na,t; I A; I K;
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Fineberg_et_al_2012
IonChannelLab Files
README.html
Kv4_csi.mod
Kv4_csiosi.mod
migliore_kaprox.mod *
migliore_kdrca1.mod *
migliore_na3.mod *
migliore_nax.mod *
csi.hoc
csin160_mod.nrn
csiosi.hoc
csiosin160_mod.nrn
Figure11C CSI.hoc
Figure11C CSIOSI.hoc
Figure11D.hoc
Figure11E.hoc
graphavailability.ses
graphvoltage.ses
iclamp250.ses
iclamp40.ses
mosinit.hoc
n160_mod.nrn *
screenshot1.png
screenshot2.png
                            
TITLE na3
: Na current for axon. No slow inact.
: M.Migliore Jul. 1997

NEURON {
	SUFFIX nax
	USEION na READ ena WRITE ina
	RANGE  gbar
	GLOBAL minf, hinf, mtau, htau,thinf, qinf
}

PARAMETER {
	gbar = 0.010   	(mho/cm2)	
								
	tha  =  -30	(mV)		: v 1/2 for act	
	qa   = 7.2	(mV)		: act slope (4.5)		
	Ra   = 0.4	(/ms)		: open (v)		
	Rb   = 0.124 	(/ms)		: close (v)		

	thi1  = -45	(mV)		: v 1/2 for inact 	
	thi2  = -45 	(mV)		: v 1/2 for inact 	
	qd   = 1.5	(mV)	        : inact tau slope
	qg   = 1.5      (mV)
	mmin=0.02	
	hmin=0.5			
	q10=2
	Rg   = 0.01 	(/ms)		: inact recov (v) 	
	Rd   = .03 	(/ms)		: inact (v)	

	thinf  = -50 	(mV)		: inact inf slope	
	qinf  = 4 	(mV)		: inact inf slope 

	ena		(mV)            : must be explicitly def. in hoc
	celsius
	v 		(mV)
}


UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)
	(pS) = (picosiemens)
	(um) = (micron)
} 

ASSIGNED {
	ina 		(mA/cm2)
	thegna		(mho/cm2)
	minf 		hinf 		
	mtau (ms)	htau (ms) 	
}
 

STATE { m h}

BREAKPOINT {
        SOLVE states METHOD cnexp
        thegna = gbar*m*m*m*h
	ina = thegna * (v - ena)
} 

INITIAL {
	trates(v)
	m=minf  
	h=hinf
}

DERIVATIVE states {   
        trates(v)      
        m' = (minf-m)/mtau
        h' = (hinf-h)/htau
}

PROCEDURE trates(vm) {  
        LOCAL  a, b, qt
        qt=q10^((celsius-24)/10)
	a = trap0(vm,tha,Ra,qa)
	b = trap0(-vm,-tha,Rb,qa)
	mtau = 1/(a+b)/qt
        if (mtau<mmin) {mtau=mmin}
	minf = a/(a+b)

	a = trap0(vm,thi1,Rd,qd)
	b = trap0(-vm,-thi2,Rg,qg)
	htau =  1/(a+b)/qt
        if (htau<hmin) {htau=hmin}
	hinf = 1/(1+exp((vm-thinf)/qinf))
}

FUNCTION trap0(v,th,a,q) {
	if (fabs(v-th) > 1e-6) {
	        trap0 = a * (v - th) / (1 - exp(-(v - th)/q))
	} else {
	        trap0 = a * q
 	}
}	

        


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