T channel currents (Vitko et al 2005)

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Accession:53965
Computer simulations predict that seven of the SNPs would increase firing of neurons, with three of them inducing oscillations at similar frequencises. 3 representative models from the paper have been submited: a wild-type (WT) recombinant Cav3.2 T-channel, and two of the mutants described in the Vitko et al., 2005 paper (C456S and R788C). See the paper for more and details.
Reference:
1 . Vitko I, Chen Y, Arias JM, Shen Y, Wu XR, Perez-Reyes E (2005) Functional characterization and neuronal modeling of the effects of childhood absence epilepsy variants of CACNA1H, a T-type calcium channel. J Neurosci 25:4844-55 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Channel/Receptor;
Brain Region(s)/Organism:
Cell Type(s):
Channel(s): I T low threshold;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Ion Channel Kinetics; Epilepsy;
Implementer(s):
Search NeuronDB for information about:  I T low threshold;
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zippedModels
Cav32_R788C
cells
README *
capump.mod *
HH2.mod *
IT2.mod
VClamp.mod *
El.oc *
leak.oc *
loc3.oc *
loc80.oc *
locD.oc *
mosinit.hoc *
R788Cep.jpg
R788Cip.jpg
re1_cc.oc *
re3_cc.oc *
re3_vc.oc *
re80_cc.oc *
re80_vc.oc *
reD_cc.oc *
reD_vc.oc *
rundemo.hoc *
                            
TITLE Low threshold calcium current
:
:   Ca++ current responsible for low threshold spikes (LTS)
:   RETICULAR THALAMUS
:   Differential equations
:
:   Model of Huguenard & McCormick, J Neurophysiol 68: 1373-1383, 1992.
:   
:   Written by Alain Destexhe, Salk Institute, Sept 18, 1992
:   
:    - Biophysical properties of the T current were from recordings of
:    - human recombinant Cav3.2 T-channel in HEK-293 cells
:    - see Vitko et al., J. Neurosci 25(19) :4844-4855, 2005
:    - Q10 and shift parameters are fixed 
:   
:
:   

INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}

NEURON {
	SUFFIX it2
	USEION ca READ cai, cao WRITE ica
	RANGE gcabar, m_inf, tau_m, h_inf, tau_h, shift
}

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

	FARADAY = (faraday) (coulomb)
	R = (k-mole) (joule/degC)
}

PARAMETER {
	v		(mV)
	celsius	= 36	(degC)
:	eca	= 120	(mV)
	gcabar	= .0008	(mho/cm2)
	shift	= 0 	(mV)
	cai	= 2.4e-4 (mM)		: adjusted for eca=120 mV
	cao	= 2	(mM)
}

STATE {
	m h
}

ASSIGNED {
	ica	(mA/cm2)
	carev	(mV)
	m_inf
	tau_m	(ms)
	h_inf
	tau_h	(ms)
	phi_m
	phi_h
}

BREAKPOINT {
	SOLVE castate METHOD cnexp
	carev = (1e3) * (R*(celsius+273.15))/(2*FARADAY) * log (cao/cai)
	ica = gcabar * m*m*h * (v-carev)
}

DERIVATIVE castate {
	evaluate_fct(v)

	m' = (m_inf - m) / tau_m
	h' = (h_inf - h) / tau_h
}

UNITSOFF
INITIAL {
:
:   Activation functions and kinetics were obtained from
:   Vitko et al., 2005 at 23-25 deg.
:   Transformation to 36 deg assuming Q10 of 5 and 3 for m and h
:   (as in Coulter et al., J Physiol 414: 587, 1989)
:
	phi_m = 5.0 ^ (12/10)
	phi_h = 3.0 ^ (12/10)

	evaluate_fct(v)

	m = m_inf
	h = h_inf
}

PROCEDURE evaluate_fct(v(mV)) { 
:
:   Time constants were obtained from Vitko, Arias, Perez-Reyes
:

	m_inf = 1.0 / ( 1 + exp(-(v+shift+52.5)/7.85) )
	h_inf = 1.0 / ( 1 + exp((v+shift+83.24)/8.51) )

	tau_m = ( 1.97 + 1.0 / ( exp((v+shift+26.5)/15.3) + exp(-(v+shift+147)/27) ) ) / phi_m
	tau_h = 16 + (1942 + exp((v+shift+161)/8.7)) / (1 + exp((v+shift+89.6)/3.7) ) / phi_h
}
UNITSON

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