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 Voltage-gated low threshold potassium current from Kv1 subunits

COMMENT

NEURON implementation of a potassium channel from Kv1.1 subunits
Kinetical scheme: Hodgkin-Huxley m^4, no inactivation

Experimental data taken from:
Human Kv1.1 expressed in xenopus oocytes: Zerr et al., J Neurosci 18, 2842, 2848, 1998
Vhalf = -28.8 +- 2.3 mV; k = 8.1+- 0.9 mV

The voltage dependency of the rate constants was approximated by:

alpha = ca * exp(-(v+cva)/cka)
beta = cb * exp(-(v+cvb)/ckb)

Parameters ca, cva, cka, cb, cvb, ckb
were determined from least square-fits to experimental data of G/Gmax(v) and tau(v).
Values are defined in the CONSTANT block.
Model includes calculation of Kv gating current

Reference: Akemann et al., Biophys. J. (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 Kv1
	USEION k READ ek WRITE ik
	NONSPECIFIC_CURRENT i
	RANGE g, gbar, ik, i , igate, nc
	GLOBAL ninf, taun
	GLOBAL gateCurrent, gunit
}

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

	ca = 0.12889 (1/ms)
	cva = 45 (mV)
	cka = -33.90877 (mV)

	cb = 0.12889 (1/ms)
      cvb = 45 (mV)
	ckb = 12.42101 (mV)

	zn = 2.7978 (1)		: valence of n-gate         
}

PARAMETER {
	gateCurrent = 0 (1)	: gating currents ON = 1 OFF = 0
	
	gbar = 0.004 (S/cm2)   <0,1e9>
	gunit = 16 (pS)		: unitary conductance 
}


ASSIGNED {
 	celsius (degC)
	v (mV)	

	ik (mA/cm2)
	i (mA/cm2)
	igate (mA/cm2) 
	ek (mV)
	g  (S/cm2)
	nc (1/cm2)			: membrane density of channel
	
	ninf (1)
	taun (ms)
	alphan (1/ms)
	betan (1/ms)
	qt (1)
}

STATE { n }

INITIAL {
	nc = (1e12) * gbar / gunit
	qt = q10^((celsius-22 (degC))/10 (degC))
	rates(v)
	n = ninf
}

BREAKPOINT {
	SOLVE states METHOD cnexp
      g = gbar * n^4 
	ik = g * (v - ek)
	igate = nc * (1e6) * e0 * 4 * zn * ngateFlip()

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

DERIVATIVE states {
	rates(v)
	n' = (ninf-n)/taun 
}

PROCEDURE rates(v (mV)) {
	alphan = alphanfkt(v)
	betan = betanfkt(v)
	ninf = alphan/(alphan+betan) 
	taun = 1/(qt*(alphan + betan))       
}

FUNCTION alphanfkt(v (mV)) (1/ms) {
	alphanfkt = ca * exp(-(v+cva)/cka) 
}

FUNCTION betanfkt(v (mV)) (1/ms) {
	betanfkt = cb * exp(-(v+cvb)/ckb)
}

FUNCTION ngateFlip() (1/ms) {
	ngateFlip = (ninf-n)/taun 
}




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