Effect of voltage sensitive fluorescent proteins on neuronal excitability (Akemann et al. 2009)

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Accession:123453
"Fluorescent protein voltage sensors are recombinant proteins that are designed as genetically encoded cellular probes of membrane potential using mechanisms of voltage-dependent modulation of fluorescence. Several such proteins, including VSFP2.3 and VSFP3.1, were recently reported with reliable function in mammalian cells. ... Expression of these proteins in cell membranes is accompanied by additional dynamic membrane capacitance, ... We used recordings of sensing currents and fluorescence responses of VSFP2.3 and of VSFP3.1 to derive kinetic models of the voltage-dependent signaling of these proteins. Using computational neuron simulations, we quantitatively investigated the perturbing effects of sensing capacitance on the input/output relationship in two central neuron models, a cerebellar Purkinje and a layer 5 pyramidal neuron. ... ". The Purkinje cell model is included in ModelDB.
Reference:
1 . Akemann W, Lundby A, Mutoh H, Knopfel T (2009) Effect of voltage sensitive fluorescent proteins on neuronal excitability. Biophys J 96:3959-76 [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: Cerebellum;
Cell Type(s): Cerebellum Purkinje cell;
Channel(s): I Na,t; I A; I K; I h; I K,Ca; I Calcium;
Gap Junctions:
Receptor(s):
Gene(s): Kv1.1 KCNA1; Kv4.3 KCND3; Kv3.3 KCNC3; Kv3.4 KCNC4; HCN1;
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s):
Implementer(s): Akemann, Walther [akemann at brain.riken.jp];
Search NeuronDB for information about:  Cerebellum Purkinje cell; I Na,t; I A; I K; I h; I K,Ca; I Calcium;
TITLE Cav2.1 (P-type) calcium channel

COMMENT

NEURON implementation of a Cav2.1 calcium channel
Kinetical scheme: Hodgkin-Huxley (m), no inactivation

Model includes a calculation of the gating current

Modified from Khaliq et al., J. Neurosci. 23(2003)4899

Reference: Akemann et al. (2009) 96:3959-3976

Laboratory for Neuronal Circuit Dynamics
RIKEN Brain Science Institute, Wako City, Japan
http://www.neurodynamics.brain.riken.jp

Date of Implementation: April 2007
Contact: akemann@brain.riken.jp

ENDCOMMENT

NEURON {
	SUFFIX Cav2
	USEION ca READ cai, cao WRITE ica
	NONSPECIFIC_CURRENT i
	RANGE pbar, ica, i, igate, nc
	GLOBAL minf, taum
	GLOBAL gateCurrent, punit 
}

UNITS {
	(mV) = (millivolt)
	(mA) = (milliamp)
	(nA) = (nanoamp)
	(pA) = (picoamp)
	(S)  = (siemens)
	(nS) = (nanosiemens)
	(pS) = (picosiemens)
	(um) = (micron)
	(molar) = (1/liter)
	(mM) = (millimolar)		
}

CONSTANT {
	e0 = 1.60217646e-19 (coulombs)
	q10 = 2.7
	F = 9.6485e4 (coulombs)
	R = 8.3145 (joule/kelvin)

	cv = 19 (mV)
	ck = 5.5 (mV)

	zm = 4.6244 (1)				: gating charge
}

PARAMETER {
	gateCurrent = 0 (1)			: gating currents ON = 1 OFF = 0
	
	pbar = 3e-5 (cm/s)
	punit = 3.290e-13 (cm3/s)		: unitary calcium permeability
	
	monovalConc = 140 (mM)
	monovalPerm = 0 (1)
}

ASSIGNED {
	celsius (degC)
	v (mV)
	cai (mM)
	cao (mM)

	ica (mA/cm2)
	i (mA/cm2)
	igate (mA/cm2)
	
	nc (1/cm2)				: membrane density of channel

      minf (1) 
	taum (ms)
	T (kelvin)
	E (volt)
	zeta (1)
	qt (1)
}

STATE { m }

INITIAL {
	nc = pbar / punit
	qt = q10^((celsius-22 (degC))/10 (degC))
	T = kelvinfkt( celsius )
	rates(v)
	m = minf
}

BREAKPOINT {
	SOLVE states METHOD cnexp
	ica = (1e3) * pbar * m * ghk(v, cai, cao, 2)
	igate = nc * (1e6) * e0 * zm * mgateFlip()

	if (gateCurrent != 0) { 
		i = igate
	}
}

DERIVATIVE states {
	rates(v)
	m' = (minf-m)/taum
}

FUNCTION ghk( v (mV), ci (mM), co (mM), z )  (coulombs/cm3) { 
	E = (1e-3) * v
      zeta = (z*F*E)/(R*T)	
	
	: ci = ci + (monovalPerm) * (monovalConc) :Monovalent permeability

	if ( fabs(1-exp(-zeta)) < 1e-6 ) {
	ghk = (1e-6) * (z*F) * (ci - co*exp(-zeta)) * (1 + zeta/2)
	} else {
	ghk = (1e-6) * (z*zeta*F) * (ci - co*exp(-zeta)) / (1-exp(-zeta))
	}
}

PROCEDURE rates( v (mV) ) {
	minf = 1 / ( 1 + exp(-(v+cv)/ck) )
	taum = (1e3) * taumfkt(v)/qt
}

FUNCTION taumfkt( v (mV) ) (s) {
	UNITSOFF
	if ( v > -50 ) {
	taumfkt = 0.000191 + 0.00376 * exp(-((v+41.9)/27.8)^2)
	} else {
	taumfkt = 0.00026367 + 0.1278 * exp(0.10327*v)
	}
	UNITSON
}

FUNCTION kelvinfkt( t (degC) )  (kelvin) {
	UNITSOFF
	kelvinfkt = 273.19 + t
	UNITSON
}

FUNCTION mgateFlip() (1/ms) {
	mgateFlip = (minf-m)/taum
}

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