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_WT
cells
README *
capump.mod *
HH2.mod *
IT2.mod
VClamp.mod *
El.oc *
Hh8.ses
hH80_2.jpg
Hh8ips2.jpg
Hh8triple.jpg
leak.oc *
loc3.oc *
loc80.oc *
locD.oc *
mosinit.hoc *
re1_cc.oc *
re3_cc.oc *
re3_vc.oc *
re80_cc.oc *
re80_vc.oc *
reD_cc.oc *
reD_vc.oc *
rundemo.hoc *
WtEP2.jpg
                            
/*----------------------------------------------------------------------------

	VOLTAGE-CLAMP SIMULATIONS OF RE CELLS
	=====================================

	- passive and structural parameters estimated from SimFit
	- electrode with adjustable series resistance
	- simulations at 36 degC
	- calcium diffusion
	- Q10=2.5
	- hyperpolarized leak of -82 mV; dc current to maintain at -65


	  ** current-clamp in dissociated RE cell with 8 compartment **


  For more details, see:

  Destexhe, A., Contreras, D., Steriade, M., Sejnowski, T.J. and Huguenard,
  J.R.  In vivo, in vitro and computational analysis of dendritic calcium
  currents in thalamic reticular neurons.  J. Neurosci. 16: 169-185, 1996.

  See also:

  http://www.cnl.salk.edu/~alain
  http://cns.fmed.ulaval.ca

----------------------------------------------------------------------------*/



//----------------------------------------------------------------------------
//  load and define general graphical procedures
//----------------------------------------------------------------------------

// xopen("$(NEURONHOME)/lib/hoc/stdrun.hoc")
load_file("nrngui.hoc")

objectvar g[20]			// max 20 graphs
ngraph = 0

proc addgraph() { local ii	// define subroutine to add a new graph
				// addgraph("variable", minvalue, maxvalue)
	ngraph = ngraph+1
	ii = ngraph-1
	g[ii] = new Graph()
	g[ii].size(tstart,tstop,$2,$3)
	g[ii].xaxis()
	g[ii].yaxis()
	g[ii].addvar($s1,1,0)
	g[ii].save_name("graphList[0].")
	graphList[0].append(g[ii])
}

if(ismenu==0) {
  nrnmainmenu()			// create main menu
  nrncontrolmenu()		// create control menu
}




//----------------------------------------------------------------------------
//  transient time
//----------------------------------------------------------------------------

trans = 200

print " "
print ">> Transient time of ",trans," ms"
print " "





//----------------------------------------------------------------------------
//  create multi-compartment geometry and insert currents
//----------------------------------------------------------------------------

xopen("cells/reD.geo")	// read geometry file

corrD = 1			// dendritic surface correction

forall { 			// insert passive current everywhere
	insert pas
	g_pas = 5e-5 * corrD	// (from simfit)
//	e_pas = -72.843		// (from simfit)
	e_pas = -82		// corrected for liquid junction potential
	cm = 1 * corrD		// (from simfit)
	Ra = 260		// (from simfit)
	L = L
}

soma {
	g_pas = 5e-5		// (from simfit)
	cm = 1			// (from simfit)

	insert hh2		// insert fast spikes
	ena = 50
	ek = -100
	vtraub_hh2 = -67	// threshold for spikes is low
	gnabar_hh2 = 0.1
	gkbar_hh2 = 0.08

}


forall {
	insert it2		// T-current everywhere
	cai = 2.4e-4 
	cao = 2 
	eca = 120 
	shift_it2 = 0		// no shift of ITs
	gcabar_it2 = corrD * 0.0002
	qm_it2 = 2.5		// low q10
	qh_it2 = 2.5

	insert cad		// calcium diffusion everywhere
	depth_cad = corrD	// NEED TO BE RESCALED
	kt_cad = 0		// no pump
	kd_cad = 1e-4
	taur_cad = 5
	cainf_cad = 2.4e-4	
}



xopen("locD.oc")	// load procedure for localizing T-current

localize(4.5e-5, 4.5e-5) 	// initial distribution of T-current


xopen("leak.oc")	// load dc current injection

access soma
add_dc(0.03)			// set 0.03 nA dc current to adjust to -65 mV







//----------------------------------------------------------------------------
//  insert electrode in the soma
//----------------------------------------------------------------------------

load_file("El.oc")		// Electrode with series resistance

access soma
objectvar El			// insert electrode
El = new Electrode()
electrodes_present=1

//
// CURRENT-CLAMP MODE
//

	soma El.stim.loc(0.5)		// put electrode in current-clamp mode
	El.stim.del = 100
	El.stim.dur = 200
	El.stim.amp = -0.3


//----------------------------------------------------------------------------
//  setup simulation parameters
//----------------------------------------------------------------------------

Dt = 0.1
npoints = 4000

objectvar Sim			// create vector of simulation points
Sim = new Vector(npoints)

dt = 0.1			// must be submultiple of Dt
tstart = trans-100
tstop = trans + npoints * Dt
runStopAt = tstop
steps_per_ms = 1/Dt
celsius = 36
v_init = -70






//----------------------------------------------------------------------------
//  add graphs
//----------------------------------------------------------------------------

addgraph("soma.v(0.5)",-120,40)
addgraph("dend1[3].v(0.5)",-120,40)  	// for dissociated cell
//addgraph("dend1[3].v(0.5)",-120,40)	// for intact cell
//addgraph("dend1[8].v(0.5)",-120,40)	// for intact cell
//addgraph("dend1[12].v(0.5)",-120,40)	// for intact cell

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