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 L-type calcium channel with high threshold for activation
: used in somatic and dendritic regions 
: 
: After Borg 
:  Updated by Maria Markaki  12/02/03

NEURON {
	SUFFIX cal
	USEION ca READ cai, eca WRITE ica
 	USEION cal WRITE ical VALENCE 2: to use it in cal-specific pump
        RANGE gcalbar, ica, po, ical
	GLOBAL inf, s_inf, tau_m
}

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


PARAMETER {     
  	ki     = 0.025  (mM)            : middle point of inactivation fct
  :	ki     = 0.01  (mM)            : middle point of inactivation fct
 :   gcalbar = 0.2e-7      (cm/s) : initialized conductance
	gcalbar = 0   (mho/cm2)  : initialized conductance
 	taumin  = 100    (ms)            : minimal value of the time cst
        vhalf = -1 (mV)       :half potential for activation 
	zeta=-4.6
	t0=1.5(ms)
	b = 0.01 	(mM)
:	b = 0.005 	(mM)
}


ASSIGNED {      : parameters needed to solve DE
        v               (mV)
 	celsius         (degC)
	cai             (mM)      : initial internal Ca++ concentration
	ica             (mA/cm2)
	eca             (mV)
	ical             (mA/cm2)
	po
        inf
	s_inf
	tau_m           (ms)
}

STATE {	
	m 
	s 
} 


INITIAL {
	rates(v,cai)
	m = inf    : initial activation parameter value
	s = s_inf
}

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

BREAKPOINT {
	SOLVE states METHOD cnexp
	po = m*m*h2(cai)
:	po = m*m*h2(cai)
	ica = (gcalbar*po+s*s*8*gcalbar)*(v-eca)
:	ica = (gcalbar*po+s*gcalbar*0.4)*ghk(v, cai, cao)
	ical = ica
}


DERIVATIVE states {
	rates(v,cai)
	m' = (inf-m)/t0
	s' = (s_inf-s)/tau_m
}



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

PROCEDURE rates(v(mV), cai(mM)) {LOCAL a, alpha2
		a = alp(v)
		inf = 1/(1+a)
		alpha2 = (cai/b)^2
		s_inf = alpha2 / (alpha2 + 1)
		tau_m = taumin+ 1(ms)*1(mM)/(cai+b)
}


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