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 decay of submembrane calcium concentration
:
: Internal calcium concentration due to calcium currents and decay.
: (decay can be viewed as simplified buffering)
:
:  This is a simple pool model of [Ca++]. 
:  cai' = drive_channel + (cainf-cai)/taur,
:  where the first term
:  drive_channel =  - (10000) * ica / (2 * FARADAY * depth)
:  describes the change caused by Ca++ inflow into a compartment
:  with volume u (u is restricted to the volume of a submembrane shell).
: (Units checked using "modlunit" -> factor 10000 needed in ca entry.)
:
:  The second is a decay term that causes [Ca++] to decay exponentially 
:  (with a time constant taur) to the baseline concentration cainf
:  Simple first-order decay or buffering:
:
:       Cai + B <-> ...
:
:   which can be written as:
:
:       dCai/dt = (cainf - Cai) / taur
:
:   where cainf is the equilibrium intracellular calcium value (usually
:   in the range of 200-300 nM) and taur is the time constant of calcium 
:   removal.  The dynamics of submembranal calcium is usually thought to
:   be relatively fast, in the 1-10 millisecond range (see Blaustein, 
:   TINS, 11: 438, 1988).
:   Or, taur >= 0.1ms (De Schutter and Bower 1994),
:       taur <= 50 ms (Traub and Llinas 1977).
:
: Written by Alain Destexhe, Salk Institute, Nov 12, 1992
:
:

NEURON {
	SUFFIX cad
	USEION ca READ ica, cai WRITE cai	
	GLOBAL depth,cainf,taur
}

UNITS {
	(molar) = (1/liter)			: moles do not appear in units
	(mM)	= (millimolar)
	(um)	= (micron)
	(mA)	= (milliamp)
	(msM)	= (ms mM)
	FARADAY = (faraday) (coulomb)
}


PARAMETER {
	depth	= .1	(um)		: depth of shell
	taur	= 2	(ms)		: rate of calcium removal
:	taur	= 4	(ms)		: rate of calcium removal
	cainf	= 2.4e-4 (mM)
:	cainf	= 100e-6(mM)
}

STATE {
	cai		(mM) 
}

:INITIAL {
:	ca = cainf
:}

ASSIGNED {
	ica		(mA/cm2)
	drive_channel	(mM/ms)
}
	
BREAKPOINT {
:	SOLVE state METHOD cnexp
	SOLVE state METHOD derivimplicit
}

DERIVATIVE state { 

	drive_channel =  - (10000) * ica / (2 * FARADAY * depth)
	if (drive_channel <= 0.) { drive_channel = 0.  }   : cannot pump inward 
         
	cai' = drive_channel + (cainf-cai)/taur
}

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