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;
: from  Migliore mycan2.mod,without deactivation
: activation gate from  Dimitri, tau midpoint-
: voltage 
: own GHK
: T-dependece from McAllister-Williams 95


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

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

	F = 96485 (coul)
	R = 8.3134 (joule/degC)
}

PARAMETER {
	v (mV)
	celsius 		(degC)
: PcanpqBar=0.7*PcaRest
	PcanpqBar=.000154 (cm/s)
: was soll ki
	ki=.00002 (mM)
	cai=5.e-5 (mM)
	cao = 10  (mM)
	q10m=11.45
	q10Ampl=2.1
}


NEURON {
	SUFFIX CAnpq
	USEION ca READ cai,cao WRITE ica
        RANGE PcanpqBar
        GLOBAL minf,taum
}

STATE {
	m
}

ASSIGNED {
	ica (mA/cm2)
        Pcanpq  (cm/s) 
        minf
        taum
}

INITIAL {
        rates(v)
        m = minf
}

UNITSOFF
BREAKPOINT {
	LOCAL qAmpl
	
	qAmpl = q10Ampl^((celsius - 21)/10)
	
	SOLVE states METHOD cnexp
	Pcanpq = qAmpl*PcanpqBar*m*m
	ica = Pcanpq*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))
	}
}

FUNCTION alpm(v(mV)) {
	:TABLE FROM -150 TO 150 WITH 200
	alpm = 0.1967*(-1.0*(v-15)+19.88)/(exp((-1.0*(v-15)+19.88)/10.0)-1.0)
}

FUNCTION betm(v(mV)) {
	:TABLE FROM -150 TO 150 WITH 200
	betm = 0.046*exp(-(v-15)/20.73)
}




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

PROCEDURE rates(v (mV)) { :callable from hoc
        LOCAL a, qm
	
        TABLE taum, minf FROM -150 TO 150 WITH 3000
        
        qm = q10m^((celsius - 22)/10)
        a = alpm(v)
        taum = 1/((a + betm(v))*qm)
	
	: lt. Dimitri
        minf = 1/(1+exp(-(v+11)/5.7)) ^0.5 
}


UNITSON











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