Amyloid beta (IA block) effects on a model CA1 pyramidal cell (Morse et al. 2010)

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Accession:87284
The model simulations provide evidence oblique dendrites in CA1 pyramidal neurons are susceptible to hyper-excitability by amyloid beta block of the transient K+ channel, IA. See paper for details.
Reference:
1 . Morse TM, Carnevale NT, Mutalik PG, Migliore M, Shepherd GM (2010) Abnormal excitability of oblique dendrites implicated in early Alzheimer's: a computational study Front. Neural Circuits 4:16 [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:
Cell Type(s): Hippocampus CA1 pyramidal cell;
Channel(s): I Na,t; I L high threshold; I N; I T low threshold; I A; I K; I h; I K,Ca;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Dendritic Action Potentials; Active Dendrites; Detailed Neuronal Models; Pathophysiology; Aging/Alzheimer`s;
Implementer(s): Carnevale, Ted [Ted.Carnevale at Yale.edu]; Morse, Tom [Tom.Morse at Yale.edu];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal cell; I Na,t; I L high threshold; I N; I T low threshold; I A; I K; I h; I K,Ca;
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CA1_abeta
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cagk.mod *
cal2.mod *
can2.mod *
cat.mod *
distr.mod *
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ipulse2.mod *
kadist.mod
kaprox.mod
kdrca1.mod
na3n.mod
naxn.mod *
zcaquant.mod
aBeta.hoc
add_ca.hoc
bAP_peak_vecs.hoc
c91662.ses
C91662_Link.txt
cond_report.hoc
control_boxes.hoc
distribute_currents.hoc
fig1.jpg
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fig2A_c91662.hoc
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fig4.jpg
fig4.ses
fig5.jpg
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figs.hoc
find_averages.hoc
fixnseg.hoc
GaspiriniEtAl2007Fig1Stimulation.ses
generate_conc_graph.hoc
gka_averager.hoc
graph_na3_kinetics.hoc
init_and_run_and_graph.hoc
leaky_distal.hoc
maxica.hoc
maxica.ses.20100525
mosinit.hoc
na3_shifter.hoc
ntc_additions.hoc
oblique_application.hoc
oblique_scaled_ka.hoc
obliques_primary_tuft.hoc
paper_fig_buttons.hoc
sectiontest.hoc
shrink_obliques.hoc
SubBranch.hoc
trigger_and_start.hoc
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TITLE n-calcium channel
: n-type calcium channel


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

	FARADAY = 96520 (coul)
	R = 8.3134 (joule/degC)
	KTOMV = .0853 (mV/degC)
}

PARAMETER {
	v (mV)
	celsius 		(degC)
	gcanbar=.0003 (mho/cm2)
	ki=.001 (mM)
	cai=50.e-6 (mM)
	cao = 2  (mM)
	q10=5
	mmin = 0.2
	hmin = 3
	a0m =0.03
	zetam = 2
	vhalfm = -14
	gmm=0.1	
}


NEURON {
	SUFFIX can
	USEION ca READ cai,cao WRITE ica
        RANGE gcanbar, ica, gcan       
        GLOBAL hinf,minf,taum,tauh
}

STATE {
	m h 
}

ASSIGNED {
	ica (mA/cm2)
        gcan  (mho/cm2) 
        minf
        hinf
        taum
        tauh
}

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

BREAKPOINT {
	SOLVE states METHOD cnexp
	gcan = gcanbar*m*m*h*h2(cai)
	ica = gcan*ghk(v,cai,cao)

}

UNITSOFF
FUNCTION h2(cai(mM)) {
	h2 = ki/(ki+cai)
}


FUNCTION ghk(v(mV), ci(mM), co(mM)) (mV) {
        LOCAL nu,f

        f = KTF(celsius)/2
        nu = v/f
        ghk=-f*(1. - (ci/co)*exp(nu))*efun(nu)
}

FUNCTION KTF(celsius (degC)) (mV) {
        KTF = ((25./293.15)*(celsius + 273.15))
}


FUNCTION efun(z) {
	if (fabs(z) < 1e-4) {
		efun = 1 - z/2
	}else{
		efun = z/(exp(z) - 1)
	}
}

FUNCTION alph(v(mV)) {
	alph = 1.6e-4*exp(-v/48.4)
}

FUNCTION beth(v(mV)) {
	beth = 1/(exp((-v+39.0)/10.)+1.)
}

FUNCTION alpm(v(mV)) {
	alpm = 0.1967*(-1.0*v+19.88)/(exp((-1.0*v+19.88)/10.0)-1.0)
}

FUNCTION betm(v(mV)) {
	betm = 0.046*exp(-v/20.73)
}

FUNCTION alpmt(v(mV)) {
  alpmt = exp(0.0378*zetam*(v-vhalfm)) 
}

FUNCTION betmt(v(mV)) {
  betmt = exp(0.0378*zetam*gmm*(v-vhalfm)) 
}

UNITSON

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

PROCEDURE rates(v (mV)) { :callable from hoc
        LOCAL a, b, qt
        qt=q10^((celsius-25)/10)
        a = alpm(v)
        b = 1/(a + betm(v))
        minf = a*b
	taum = betmt(v)/(qt*a0m*(1+alpmt(v)))
	if (taum<mmin/qt) {taum=mmin/qt}
        a = alph(v)
        b = 1/(a + beth(v))
        hinf = a*b
:	tauh=b/qt
	tauh= 80
	if (tauh<hmin) {tauh=hmin}
}

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