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;
TITLE T-calcium channel
: gate h, taus Kloeckner 99 and Chemin 2002; 
: gate  m: Lee, Dand 99
: q10s  Coulter 89

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 = 6.3	(degC)

	PcaTbar = .000011 (cm/s)
	cai (mM)
	cao (mM)
	q10Ampl=3.3
	q10m=3.55
	q10h=2.8
}


NEURON {
	SUFFIX cat
	USEION ca READ cai,cao WRITE ica
        RANGE PcaTbar,cai
}

STATE {
	m h 
}

ASSIGNED {
	ica (mA/cm2)
        PcaT (cm/s)
}

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

UNITSOFF
BREAKPOINT {
	SOLVE states METHOD cnexp
	PcaT = PcaTbar*m*m*h
	ica = PcaT*ghk(v,cai,cao)

}

DERIVATIVE states {	: exact when v held constant
	m' = (minf(v) - m)/m_tau(v)
	h' = (hinf(v) - h)/h_tau(v)
}




FUNCTION ghk(v(mV), ci(mM), co(mM)) (mV) {
        LOCAL a, qtAmpl
	
	qtAmpl=q10Ampl^((celsius-23)/10)

        a=2*F*v/(R*(celsius+273.15)*1000)
	
        ghk=qtAmpl*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 hinf(v(mV)) 
{       TABLE FROM -150 TO 150 WITH 3000 :Mitti 
	hinf = 1/(1+exp((v+72)/3.7))
}

FUNCTION minf(v(mV)) {
	TABLE FROM -150 TO 150 WITH 3000 :Mitti
        minf = (1/(1+exp(-(v+31.4)/8.8)))^0.5
}

FUNCTION m_tau(v(mV)) (ms) {
	LOCAL f1,f2, qtm
	
        TABLE FROM -150 TO 150 WITH 3000 :Mitti
        
	qtm=q10m^((celsius-23)/10)
	
	f1=1/(1+exp(-(v-7.63)/28.47))+0.01
	f2=62.82/(1+exp((v+37.02)/5.27))+3.78

	m_tau=f1*f2/qtm
}

FUNCTION h_tau(v(mV)) (ms) {
	LOCAL alphah, localhinf,qth
	
        TABLE FROM -150 TO 150 WITH 3000 :Mitti
        
	qth=q10h^((celsius-23)/10)
	
	localhinf = 1/(1+exp((v+72)/3.7))
	
	alphah=0.0021/(1+exp((v+65.77)/4.32))
	
	h_tau = localhinf/(qth*alphah)
}

UNITSON








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