CA1 pyramidal neuron: functional significance of axonal Kv7 channels (Shah et al. 2008)

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Accession:112546
The model used in this paper confirmed the experimental findings suggesting that axonal Kv7 channels are critically and uniquely required for determining the inherent spontaneous firing of hippocampal CA1 pyramids, independently of alterations in synaptic activity. The model predicts that the axonal Kv7 density could be 3-5 times that at the soma.
Reference:
1 . Shah MM, Migliore M, Valencia I, Cooper EC, Brown DA (2008) Functional significance of axonal Kv7 channels in hippocampal pyramidal neurons. Proc Natl Acad Sci U S A 105:7869-74 [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): Hippocampus CA1 pyramidal GLU cell;
Channel(s): I Na,t; I T low threshold; I A; I K; I M; I Calcium;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Action Potential Initiation; Detailed Neuronal Models; Axonal Action Potentials; Action Potentials;
Implementer(s): Migliore, Michele [Michele.Migliore at Yale.edu];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; I Na,t; I T low threshold; I A; I K; I M; I Calcium;
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km
readme.html
cacumm.mod *
cagk.mod
cal2.mod
can2.mod
cat.mod *
h.mod *
kadist.mod *
KahpM95.mod *
kaprox.mod *
kdrca1.mod *
km.mod *
na3n.mod *
naxn.mod *
fig4a.hoc
fixnseg.hoc *
geo9068802.hoc *
mosinit.hoc *
screenshot.jpg
                            
load_file("nrngui.hoc")
cvode_active(1)

dist=7
rel=0.5

numbasal=70

xopen("geo9068802.hoc")             // geometry file
xopen("fixnseg.hoc")           

Rm = 28000
Cm    = 1
RaAll= 150
RaAx = 50

Vrest = -65
dt = 0.1
gna =  .045
AXONM = 3
gkdr = 0.06
celsius = 35.0  
ka =  0.04
ghd=0.00005
gkm=0.02
gcat=0.0001
gahp=0.00001

objref g, b,c, stim, s, rsyn, nc, m, gt, gk

forsec "axon" {insert pas e_pas=Vrest g_pas = 1/Rm Ra=RaAx cm=Cm}
forsec "soma" {insert pas e_pas=Vrest g_pas = 1/Rm Ra=RaAll cm=Cm}
forsec "dendrite"{insert pas e_pas=Vrest g_pas = 1/Rm Ra=RaAll cm=Cm}
forsec "user5" {insert pas e_pas=Vrest g_pas = 1/Rm Ra=RaAll cm=Cm}

access soma

freq=50
geom_nseg()
distance()

tstop=500

b = new VBox()
b.intercept(1)
g = new Graph()
g.size(0,tstop,-70,20)
g.xaxis(1)
g.exec_menu("10% Zoom out")
g.addexpr("v_soma","soma.v(rel)",1,1, 0.2,0.9,2)
xpanel("",1)
xbutton("fig.4(i)", "runi()")
xbutton("fig.4(ii)", "runii()")
xbutton("fig.4(iii)", "runiii()")
xbutton("fig.4(iv)", "runiv()")
xpanel()
b.intercept(0)
b.map()

forsec "axon" {   
		insert km gbar_km=gkm
                insert nax gbar_nax=gna*AXONM	
                insert kdr gkdrbar_kdr=gkdr*AXONM
                insert kap gkabar_kap = ka
}

forsec "soma" {  
		insert km gbar_km=gkm
		insert hd ghdbar_hd=0	
                insert na3 gbar_na3=gna*AXONM
                insert kdr gkdrbar_kdr=gkdr*AXONM
                insert kap gkabar_kap = ka
                insert cat  gcatbar_cat=gcat
		insert cacum tau_cacum=100 depth_cacum=diam/2
		insert KahpM95 gbar_KahpM95 = gahp 
}

for i=0, numbasal-1 dendrite[i] {
                insert na3 gbar_na3=0
                insert cat  gcatbar_cat=gcat
		insert cacum tau_cacum=100 depth_cacum=diam/2
		insert KahpM95 gbar_KahpM95 = gahp 
}

                
forsec "apical_dendrite" {
		insert hd ghdbar_hd=ghd	
                insert na3 gbar_na3=gna
                insert kdr gkdrbar_kdr=gkdr
		insert kap gkabar_kap=0
		insert kad gkabar_kad=0
		insert cacum tau_cacum=100 depth_cacum=diam/2
		insert KahpM95 gbar_KahpM95 = gahp 
                insert cat  gcatbar_cat=gcat

		for (x,0) { xdist = distance(x)
                	ghdbar_hd(x) = ghd*(1+3*xdist/100)
                		if (xdist > 100){
                        		gkabar_kad(x) = ka*(1+xdist/100)
                			} else {
                        		gkabar_kap(x) = ka*(1+xdist/100)
               				}
		}
}

forsec "user5" {
		insert hd ghdbar_hd=ghd	
                insert na3 gbar_na3=gna
                insert kdr gkdrbar_kdr=gkdr
		insert kap gkabar_kap=0
		insert kad gkabar_kad=0
		insert cacum tau_cacum=100 depth_cacum=diam/2
                insert cat  gcatbar_cat=gcat
		insert KahpM95 gbar_KahpM95 = gahp 

		for (x,0) { xdist = distance(x)
                	ghdbar_hd(x) = ghd*(1+3*xdist/100)
                		if (xdist > 100){
                        		gkabar_kad(x) = ka*(1+xdist/100)
                			} else {
                        		gkabar_kap(x) = ka*(1+xdist/100)
               				}
		}
}

proc init() {
	t=0
        forall {
        v=Vrest
        if (ismembrane("nax") || ismembrane("na3")) {ena=55}
        if (ismembrane("KahpM95") || ismembrane("kap") || ismembrane("kad")) {ek=-90}
        if (ismembrane("hd") ) {ehd_hd=-30}
	}
	finitialize(Vrest)
        fcurrent()

        forall {
	for (x) {
	if (ismembrane("na3")||ismembrane("nax")){e_pas(x)=v(x)+(ina(x)+ik(x))/g_pas(x)}
	if (ismembrane("hd")) {e_pas(x)=e_pas(x)+i_hd(x)/g_pas(x)}
	if (ismembrane("cat")){e_pas(x)=e_pas(x)+ica(x)/g_pas(x)}
		}
	}
	cvode.re_init()
	cvode.event(tstop)
	access soma
	g.begin()
}

objref playvec1, playvec2
playvec1 = new Vector()
playvec1.append(0, 50, 120)
playvec2 = playvec1.c.indgen()
playvec1.play("f($1)", playvec1, playvec2, 1)
proc f() {
	if (t < 50) {
		axon.gbar_km=factor*gkm
		soma.gbar_km=gkm
	}else if (t>=50 && t<120) {
		axon.gbar_km=factor*gkm-gkm*factor*(t-50)/70 
		soma.gbar_km=gkm-gkm*(t-50)/70 
	}else{
		axon.gbar_km=0
		soma.gbar_km=0
	}
}

proc advance() {
	fadvance()
	g.plot(t)
	g.flush()
	doNotify()
}

proc runi() {
factor=2
soma.gbar_km=gkm
axon.gbar_km=gkm*factor
run()
}

proc runii() {
factor=3
soma.gbar_km=gkm
axon.gbar_km=gkm*factor
run()
}

proc runiii() {
factor=4
soma.gbar_km=gkm
axon.gbar_km=gkm*factor
run()
}

proc runiv() {
factor=6
soma.gbar_km=gkm
axon.gbar_km=gkm*factor
run()
}


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