Action Potential initiation and backpropagation in Neocortical L5 Pyramidal Neuron (Hu et al. 2009)

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Accession:123897
"...Previous computational studies have yielded conflicting conclusions about the role of Na+ channel density and biophysical properties in action potential initiation as a result of inconsistent estimates of channel density. Our modeling studies integrated the immunostaining and electrophysiological results and showed that the lowest threshold for action potential initiation at the distal AIS was largely determined by the density of low-threshold Nav1.6 channels ... Distinct from the function of Nav1.6 channel, the Nav1.2 channel may control action potential backpropagation because of its high density at the proximal AIS and high threshold. ... In conclusion, distal AIS accumulation of Nav1.6 channels determines the low threshold for action potential initiation; whereas proximal AIS accumulation of Nav1.2 channels sets the threshold for the generation of somatodendritic potentials and ensures action potential backpropagation to the soma and dendrites. Thus, Nav1.6 and Nav1.2 channels serve distinct functions in action potential initiation and backpropagation."
Reference:
1 . Hu W, Tian C, Li T, Yang M, Hou H, Shu Y (2009) Distinct contributions of Na(v)1.6 and Na(v)1.2 in action potential initiation and backpropagation. Nat Neurosci 12:996-1002 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Axon; Channel/Receptor;
Brain Region(s)/Organism:
Cell Type(s): Neocortex U1 L2/6 pyramidal intratelencephalic GLU cell; Neocortex U1 L5B pyramidal pyramidal tract GLU cell;
Channel(s): I K; I M; I K,Ca; I Sodium; I Calcium;
Gap Junctions:
Receptor(s):
Gene(s): Nav1.2 SCN2A; Nav1.6 SCN8A;
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Action Potential Initiation; Ion Channel Kinetics; Axonal Action Potentials;
Implementer(s): Hu, Wenqin [huwenqin at ion.ac.cn]; Hou, Han [hh at ion.ac.cn];
Search NeuronDB for information about:  Neocortex U1 L5B pyramidal pyramidal tract GLU cell; Neocortex U1 L2/6 pyramidal intratelencephalic GLU cell; I K; I M; I K,Ca; I Sodium; I Calcium;
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HuEtAl2009
mechanism
ca.mod *
cad.mod *
gabaa.mod *
kca.mod *
km.mod *
kv.mod *
na.mod *
na12.mod *
na16.mod *
mosinit.hoc
                            
COMMENT

km.mod

Potassium channel, Hodgkin-Huxley style kinetics
Based on I-M (muscarinic K channel)
Slow, noninactivating

Author: Zach Mainen, Salk Institute, 1995, zach@salk.edu
	
ENDCOMMENT

INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}

NEURON {
	SUFFIX km
	USEION k READ ek WRITE ik
	RANGE n, gk, gbar
	RANGE ninf, ntau
	GLOBAL Ra, Rb
	GLOBAL q10, temp, tadj, vmin, vmax
}

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

PARAMETER {
	gbar = 10   	(pS/um2)	: 0.03 mho/cm2
	v 		(mV)
								
	tha  = -30	(mV)		: v 1/2 for inf
	qa   = 9	(mV)		: inf slope		
	
	Ra   = 0.001	(/ms)		: max act rate  (slow)
	Rb   = 0.001	(/ms)		: max deact rate  (slow)

	dt		(ms)
	celsius		(degC)
	temp = 23	(degC)		: original temp 	
	q10  = 2.3			: temperature sensitivity

	vmin = -120	(mV)
	vmax = 100	(mV)
} 


ASSIGNED {
	a		(/ms)
	b		(/ms)
	ik 		(mA/cm2)
	gk		(pS/um2)
	ek		(mV)
	ninf
	ntau (ms)	
	tadj
}
 

STATE { n }

INITIAL { 
	trates(v)
	n = ninf
}

BREAKPOINT {
        SOLVE states
	gk = tadj*gbar*n
	ik = (1e-4) * gk * (v - ek)
} 

LOCAL nexp

PROCEDURE states() {   :Computes state variable n 
        trates(v)      :             at the current v and dt.
        n = n + nexp*(ninf-n)
        VERBATIM
        //return 0;
        ENDVERBATIM
}

PROCEDURE trates(v) {  :Computes rate and other constants at current v.
                      :Call once from HOC to initialize inf at resting v.
        LOCAL tinc
        TABLE ninf, nexp
	DEPEND dt, celsius, temp, Ra, Rb, tha, qa
	
	FROM vmin TO vmax WITH 199

	rates(v): not consistently executed from here if usetable_hh == 1

        tadj = q10^((celsius - temp)/10)

        tinc = -dt * tadj
        nexp = 1 - exp(tinc/ntau)
}


PROCEDURE rates(v) {  :Computes rate and other constants at current v.
                      :Call once from HOC to initialize inf at resting v.

        a = Ra * (v - tha) / (1 - exp(-(v - tha)/qa))
        b = -Rb * (v - tha) / (1 - exp((v - tha)/qa))
        ntau = 1/(a+b)
	ninf = a*ntau
}


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