Axonal NaV1.6 Sodium Channels in AP Initiation of CA1 Pyramidal Neurons (Royeck et al. 2008)

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Accession:115356
"... We show that the Na+ channel NaV1.6 displays a striking aggregation at the AIS of cortical neurons. ... In combination with simulations using a realistic computer model of a CA1 pyramidal cell, our results imply that a hyperpolarized voltage-dependence of activation of AIS NaV1.6 channels is important both in determining spike threshold and localizing spike initiation to the AIS. ... These results suggest that NaV1.6 subunits at the AIS contribute significantly to its role as spike trigger zone and shape repetitive discharge properties of CA1 neurons."
Reference:
1 . Royeck M, Horstmann MT, Remy S, Reitze M, Yaari Y, Beck H (2008) Role of axonal NaV1.6 sodium channels in action potential initiation of CA1 pyramidal neurons. J Neurophysiol 100:2361-80 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism: Hippocampus;
Cell Type(s): Hippocampus CA1 pyramidal GLU cell;
Channel(s): I Na,p; I Na,t; I L high threshold; I N; I T low threshold; I p,q; I A; I K; I M; I h; I K,Ca; I Calcium; I Q;
Gap Junctions:
Receptor(s):
Gene(s): Nav1.6 SCN8A;
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Action Potential Initiation; Ion Channel Kinetics; Temporal Pattern Generation;
Implementer(s): Horstmann, Marie-Therese [mhorstma at uni-bonn.de];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; I Na,p; I Na,t; I L high threshold; I N; I T low threshold; I p,q; I A; I K; I M; I h; I K,Ca; I Calcium; I Q;
: CA-R-channel, gates Dimitri
: taus from Randall 97
: own GHK
: T-dependence from McAllister-Williams 95


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

: hier eigene Befehle
        (molar) = (1/liter)
        (mM) = (millimolar)

	FARADAY = 96520 (coul)
	R = 8.3134 (joule/degC)
	KTOMV = .0853 (mV/degC)
	F = 96485 (coul)
}

PARAMETER {
	v (mV)
	celsius 		(degC)

	PcaRbar = .000044 (cm/s)
	ki=.001 (mM)
	cai=5.e-5 (mM)
	cao = 10  (mM)
	
	q10m=11.45
	q10Ampl=2.1
	q10h=3
}


NEURON {
	SUFFIX car
	USEION ca READ cai,cao WRITE ica
        RANGE PcaRbar   
        GLOBAL hinf,minf,taum,tauh
}

STATE {
	m h 
}

ASSIGNED {
	ica (mA/cm2)
        PcaR  (cm/s) 
        minf
        hinf
        taum
        tauh
}

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

UNITSOFF
BREAKPOINT {
        LOCAL qAmpl
	qAmpl = q10Ampl^((celsius - 21)/10)
	SOLVE states METHOD cnexp
	PcaR = PcaRbar*m*h
	
	ica = PcaR*qAmpl*ghk(v,cai,cao)

}

FUNCTION ghk(v(mV), ci(mM), co(mM)) (mV) {
        LOCAL a

        a=2*F*v/(R*(celsius+273.15)*1000)
	
        ghk=2*F/1000*(co - ci*exp(a))*func(a)
}


FUNCTION func(a) {
	if (fabs(a) < 1e-4) {
		func = -1 + a/2
	}else{
		func = a/(1-exp(a))
	}
}



DERIVATIVE states {     : exact when v held constant; integrates over dt step
        rates(v)
        m' = (minf - m)/taum
        h' = (hinf - h)/tauh
}

PROCEDURE rates(v (mV)) { :callable from hoc
	LOCAL alpham, f1,f2,f3,qm,qh
	
        TABLE taum, tauh, minf, hinf FROM -150 TO 150 WITH 3000
        
	qm = q10m^((celsius - 21)/10)
	qh = q10h^((celsius-21)/10)
	
	: Dimitri
	minf = 1/(1+exp(-(v+15)/5.8))
	hinf = 1/(1+exp((v+78.7)/14.5))
	
	f1=1/(1+exp(-(v+15.2)/4.29))+0.0222
	f2=15.244/(1+exp((v+13.44)/8.61))+0.511
	f3=f1*f2
        taum = f3/qm
	
        f1=1/(1+exp(-(v+49.8)/2.64))
	f2=45.11/(1+exp(v/8.92))
	f3=f1*f2+22.7
	
        tauh = f3/qh
}


UNITSON











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