CA1 pyramidal neurons: effects of a Kv7.2 mutation (Miceli et al. 2009)

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Accession:118986
NEURON mod files from the paper: Miceli et al, Neutralization of a unique, negatively-charged residue in the voltage sensor of K(V)7.2 subunits in a sporadic case of benign familial neonatal seizures, Neurobiol Dis., in press (2009). In this paper, the model revealed that the gating changes introduced by a mutation in K(v)7.2 genes encoding for the neuronal KM current in a case of benign familial neonatal seizures, increased cell firing frequency, thereby triggering the neuronal hyperexcitability which underlies the observed neonatal epileptic condition.
Reference:
1 . Miceli F, Soldovieri MV, Lugli L, Bellini G, Ambrosino P, Migliore M, del Giudice EM, Ferrari F, Pascotto A, Taglialatela M (2009) Neutralization of a unique, negatively-charged residue in the voltage sensor of K V 7.2 subunits in a sporadic case of benign familial neonatal seizures. Neurobiol Dis 34:501-10 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Dendrite;
Brain Region(s)/Organism: Hippocampus;
Cell Type(s): Hippocampus CA1 pyramidal cell;
Channel(s): I Na,t; I T low threshold; I A; I K; I M; I h;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Activity Patterns; Ion Channel Kinetics; Active Dendrites; Detailed Neuronal Models; Action Potentials;
Implementer(s): Migliore, Michele [Michele.Migliore at Yale.edu];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal cell; I Na,t; I T low threshold; I A; I K; I M; I h;
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mutant
readme.html
cacumm.mod *
cat.mod *
h.mod *
kadist.mod *
KahpM95.mod *
kaprox.mod *
kdrca1.mod *
kmquad.mod
kmtwt.mod
na3n.mod *
naxn.mod *
fig6a.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")           

Cm    = 0.75
Rm = 28000/Cm
RaAll= 500
RaAx = 50

Vrest = -65
dt = 0.1
gna =  .045
AXONM = 3
gkdr = 0.02
celsius = 35.0  
ka =  0.03
ghd=0.00001
gkm=0.006
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()

stim = new IClamp(.5)
stim.del=5
stim.dur=400
stim.amp=0.47

tstop=500
flag=0

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)
xcheckbox("mutant   ",&flag)
xbutton("run", "run()")
xpanel()
b.intercept(0)
b.map()



forsec "axon" {   
		insert kmtwt 
		insert kmtquad
                insert nax gbar_nax=gna*AXONM	
                insert kdr gkdrbar_kdr=gkdr*AXONM
                insert kap gkabar_kap = ka
}

forsec "soma" {  
		insert kmtwt
		insert kmtquad 
		insert hd ghdbar_hd=ghd	
                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
	if (flag) {perc=100} else {perc=0}
	forsec "axon" {   
		gbar_kmtwt=4*gkm*(100-perc)/100
		gbar_kmtquad=4*gkm*perc/100
	}

	forsec "soma" {  
		gbar_kmtwt=gkm*(100-perc)/100
		gbar_kmtquad=gkm*perc/100
	}

        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()
}

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


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