Firing neocortical layer V pyramidal neuron (Reetz et al. 2014; Stadler et al. 2014)

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Accession:168148
Neocortical Layer V model with firing behaviour adjusted to in vitro observations. The model was used to investigate the effects of IFN and PKC on the excitability of neurons (Stadler et al 2014, Reetz et al. 2014). The model contains new channel simulations for HCN1, HCN2 and the big calcium dependent potassium channel BK.
References:
1 . Stadler K, Bierwirth C, Stoenica L, Battefeld A, Reetz O, Mix E, Schuchmann S, Velmans T, Rosenberger K, Bräuer AU, Lehnardt S, Nitsch R, Budt M, Wolff T, Kole MH, Strauss U (2014) Elevation in type I interferons inhibits HCN1 and slows cortical neuronal oscillations. Cereb Cortex 24:199-210 [PubMed]
2 . Reetz O, Stadler K, Strauss U (2014) Protein kinase C activation mediates interferon-ß-induced neuronal excitability changes in neocortical pyramidal neurons. J Neuroinflammation 11:185 [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: Neocortex;
Cell Type(s): Neocortex V1 L6 pyramidal corticothalamic GLU cell;
Channel(s): I Na,p; I Na,t; I L high threshold; I A; I K; I M; I h; I K,Ca; I Sodium; I Calcium; I Mixed; I Potassium; I Q;
Gap Junctions:
Receptor(s):
Gene(s): HCN1; HCN2;
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Activity Patterns; Detailed Neuronal Models; Action Potentials; Signaling pathways;
Implementer(s): Stadler, Konstantin [konstantin.stadler at ntnu.no];
Search NeuronDB for information about:  Neocortex V1 L6 pyramidal corticothalamic GLU cell; I Na,p; I Na,t; I L high threshold; I A; I K; I M; I h; I K,Ca; I Sodium; I Calcium; I Mixed; I Potassium; I Q;
TITLE large-conductance calcium-activated potassium channel (BK)
	:Mechanism according to Gong et al 2001 and Womack&Khodakakhah 2002,
	:adapted for Layer V cells on the basis of Benhassine&Berger 2005.
	:NB: concentrations in mM
	
NEURON {
	SUFFIX kBK
	USEION k READ ek WRITE ik
	USEION ca READ cai
	RANGE gpeak, gkact, caPh, caPk, caPmax, caPmin
	RANGE caVhh, CaVhk, caVhmax, caVhmin, k, tau
}


UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)
	(molar) = (1/liter)
	(mM) 	= (millimolar)
}


PARAMETER {
		:maximum conductance (Benhassine 05)
	gpeak   = 268e-4	(mho/cm2) <0, 1e9>
	
	                                    : Calcium dependence of opening probability (Gong 2001)
	caPh    = 2e-3     (mM)             : conc. with half maximum open probaility
	caPk    = 1                         : Steepness of calcium dependence curve
	caPmax  = 1                         : max and
	caPmin  = 0                         : min open probability
		
	                                    : Calcium dependence of Vh shift (Womack 2002)
	caVhh   = 2e-3    (mM)              : Conc. for half of the Vh shift
	caVhk   = -0.94208                  : Steepness of the Vh-calcium dependence curve
	caVhmax = 155.67 (mV)               : max and
	caVhmin = -46.08 (mV)               : min Vh
	
	                                    : Voltage dependence of open probability (Gong 2001)
	                                    : must not be zero
	k       = 17	(mV)
	
	                                    : Timeconstant of channel kinetics
	                                    : no data for a description of a calcium&voltage dependence
	                                    : some points (room temp) in Behassine 05 & Womack 02
	tau     = 1 (ms) <1e-12, 1e9>
	scale   = 100                       : scaling to incorporate higher ca conc near ca channels
        		

} 	


ASSIGNED {
	v 		(mV)
	ek		(mV)
	ik 		(mA/cm2)
    	cai  		(mM)
	caiScaled	(mM)
	pinf		(1)
}


STATE {
        p
}

BREAKPOINT {
	SOLVE states METHOD cnexp
	ik = gpeak*p* (v - ek)
}

DERIVATIVE states {     
        rate(v, cai)
        p' =  (pinf - p)/tau
}

INITIAL {     
        rate(v, cai)
        p = pinf
}

PROCEDURE rate(v(mV), ca(mM))  {
        caiScaled = ca*scale	
        pinf = P0ca(caiScaled) / ( 1 + exp( (Vhca(caiScaled)-v)/k ) )
}

FUNCTION P0ca(ca(mM)) (1) {
		
	if (ca < 1E-18) { 		:check for division by zero		
	P0ca = caPmin
	} else {
	P0ca = caPmin + ( (caPmax - caPmin) / ( 1 + (caPh/ca)^caPk ))
	}
}

FUNCTION Vhca(ca(mM)) (mV) {
		
	if (ca < 1E-18) {		:check for division by zero
	Vhca = caVhmax
	} else {
	Vhca = caVhmin + ( (caVhmax - caVhmin ) / ( 1 + ((caVhh/ca)^caVhk)) )
	}
}	

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