Modelling reduced excitability in aged CA1 neurons as a Ca-dependent process (Markaki et al. 2005)

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Accession:119266
"We use a multi-compartmental model of a CA1 pyramidal cell to study changes in hippocampal excitability that result from aging-induced alterations in calcium-dependent membrane mechanisms. The model incorporates N- and L-type calcium channels which are respectively coupled to fast and slow afterhyperpolarization potassium channels. Model parameters are calibrated using physiological data. Computer simulations reproduce the decreased excitability of aged CA1 cells, which results from increased internal calcium accumulation, subsequently larger postburst slow afterhyperpolarization, and enhanced spike frequency adaptation. We find that aging-induced alterations in CA1 excitability can be modelled with simple coupling mechanisms that selectively link specific types of calcium channels to specific calcium-dependent potassium channels."
Reference:
1 . Markaki M, Orphanoudakis S, Poirazi P (2005) Modelling reduced excitability in aged CA1 neurons as a calcium-dependent process Neurocomputing 65-66:305-314
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 A; I K; I M; I K,Ca; I R;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Activity Patterns; Aging/Alzheimer`s;
Implementer(s):
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; I Na,p; I Na,t; I L high threshold; I N; I A; I K; I M; I K,Ca; I R;
TITLE N-type calcium channel 
: used in somatic and dendritic regions 
: After Borg 
:  Updated by Maria Markaki  03/12/03

NEURON {
	SUFFIX can
	USEION ca READ cai, eca WRITE ica 
 	USEION can WRITE ican VALENCE 2: to use it in can-specific pump
        RANGE gcalbar, ica, po, ican
	GLOBAL hinf, minf, s_inf
}

UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)
	(molar) = (1/liter)
	(mM) =	(millimolar)
	FARADAY = (faraday) (coulomb)
	R = (k-mole) (joule/degC)
}

PARAMETER {           :parameters that can be entered when function is called in cell-setup 
:	gcalbar = 0.2e-7   (cm/s)  : initialized conductance
	gcalbar = 0   (mho/cm2)  : initialized conductance
  	ki     = 0.025  (mM)            :test middle point of inactivation fct
  :	ki     = 0.01  (mM)            :test middle point of inactivation fct
	zetam = -3.4
	zetah = 2
	vhalfm =-21 (mV)
	vhalfh =-40 (mV)
	tm0=1.5(ms)
	th0=75(ms)
:	taumin  = 10    (ms)            : minimal value of the time cst
	taumin  = 2    (ms)            : minimal value of the time cst
}



ASSIGNED {     : parameters needed to solve DE
	v            (mV)
	celsius      (degC)
	ica          (mA/cm2)
	ican		(mA/cm2)
	po
	cai          (mM)       :5e-5 initial internal Ca++ concentration
	eca             (mV)
        minf
        hinf
	s_inf
}


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



STATE {	
	m 
	h 
	s
}  

INITIAL {
:	rates(v)
	rates(v,cai)
        m = minf
        h = hinf
	s = s_inf
}

BREAKPOINT {
	SOLVE states METHOD cnexp
	po = m*m*h
:	po = s*m*m
:	ica = gcalbar *po*h2(cai) * ghk(v,cai,cao)
 	ica = gcalbar *po*h2(cai) * (v - eca)
	ican = ica

}


FUNCTION ghk(v(mV), ci(mM), co(mM)) (.001 coul/cm3) {
	LOCAL z, eci, eco
	z = (1e-3)*2*FARADAY*v/(R*(celsius+273.15))
	eco = co*efun(z)
	eci = ci*efun(-z)
	:high cao charge moves inward
	:negative potential charge moves inward
	ghk = (.001)*2*FARADAY*(eci - eco)
}

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

DERIVATIVE states {
:	rates(v)
	rates(v,cai)
	m' = (minf -m)/tm0
	h'=  (hinf - h)/th0
	s' = (s_inf-s)/taumin
}


:PROCEDURE rates(v (mV)) { 
PROCEDURE rates(v (mV), cai(mM)) { 
        LOCAL a, b, alpha2
        
	a = alpm(v)
	minf = 1/(1+a)
        
        b = alph(v)
	hinf = 1/(1+b)
	alpha2 = (ki/cai)^2
	s_inf = alpha2 / (alpha2 + 1)
}




FUNCTION alpm(v(mV)) {
UNITSOFF
  alpm = exp(1.e-3*zetam*(v-vhalfm)*9.648e4/(8.315*(273.16+celsius))) 
UNITSON
}

FUNCTION alph(v(mV)) {
UNITSOFF
  alph = exp(1.e-3*zetah*(v-vhalfh)*9.648e4/(8.315*(273.16+celsius))) 
UNITSON
}


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