Nav1.6 sodium channel model in globus pallidus neurons (Mercer et al. 2007)

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Accession:105385
Model files for the paper Mercer JN, Chan CS, Tkatch T, Held J, Surmeier DJ. Nav1.6 sodium channels are critical to pacemaking and fast spiking in globus pallidus neurons.,J Neurosci. 2007 Dec 5;27(49):13552-66.
Reference:
1 . Mercer JN, Chan CS, Tkatch T, Held J, Surmeier DJ (2007) Nav1.6 sodium channels are critical to pacemaking and fast spiking in globus pallidus neurons. J Neurosci 27:13552-66 [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:
Cell Type(s): Globus pallidus neuron;
Channel(s): I Na,p; I Na,t; I K; I h; I K,Ca; I Sodium; I Calcium; I Potassium;
Gap Junctions:
Receptor(s):
Gene(s): Nav1.6 SCN8A;
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Action Potential Initiation; Action Potentials; Parkinson's;
Implementer(s): Held, Joshua [j-held at northwestern.edu];
Search NeuronDB for information about:  I Na,p; I Na,t; I K; I h; I K,Ca; I Sodium; I Calcium; I Potassium;
:Migliore file Modify by Maciej Lazarewicz (mailto:mlazarew@gmu.edu) May/16/2001

TITLE Calcium ion accumulation and diffusion
: The internal coordinate system is set up in PROCEDURE coord_cadifus()
: and must be executed before computing the concentrations.
: The scale factors set up in this procedure do not have to be recomputed
: when diam1 or DFree are changed.
: The amount of calcium in an annulus is ca[i]*diam1^2*vol[i] with
: ca[0] being the second order correct concentration at the exact edge
: and ca[NANN-1] being the concentration at the exact center

NEURON {
	SUFFIX ca_gp
	USEION ca READ cao, cai, ica WRITE cai, ica
	RANGE ipump,last_ipump,test
	GLOBAL DFree, k1buf, k2buf, k1, k2, k3, k4, totpump, totbuf
	GLOBAL vol, Buffer0
}

DEFINE NANN  4

UNITS {
        (mol)   = (1)
	(molar) = (1/liter)
	(mM)	= (millimolar)
	(um)	= (micron)
	(mA)	= (milliamp)
	FARADAY = (faraday)	(10000 coulomb)
	PI	= (pi) 		(1)
}

PARAMETER {
	DFree	= .6	(um2/ms)
	diam 	= 1	(um)
	cao		(mM)
	ica		(mA/cm2)
	k1buf 	= 500	(/mM-ms)
	k2buf 	= 0.5	(/ms)
        k1	= 1.05e10 (um3/s)
        k2	= 50.e7 (/s)	: k1*50.e-3
        k3	= 1.e10 (/s)	: k1
        k4	= 5.e6	(um3/s)	: k1*5.e-4
	totpump	= 2	(mol/cm2)
	totbuf	= 0.1	(mM)
}

CONSTANT { volo=1  (liter)}

ASSIGNED {
	area		(um2)
	test
	cai		(mM)
	vol[NANN]	(1)	: gets extra cm2 when multiplied by diam^2
	ipump           (mA/cm2)
	last_ipump	(mA/cm2)
}

STATE {
	ca[NANN]	(mM) <1.e-5> : ca[0] is equivalent to cai
	CaBuffer[NANN]  (mM)
	Buffer[NANN]    (mM)
        pump            (mol/cm2) <1.e-3>
        pumpca          (mol/cm2) <1.e-15>

}

BREAKPOINT {
	SOLVE state METHOD sparse
	last_ipump=ipump
	ica = ipump
	test = 0
}

LOCAL coord_done

INITIAL {
	if (coord_done == 0) {
		coord_done = 1
		coord()
	}
	: note Buffer gets set to Buffer0 automatically
	: and CaBuffer gets set to 0 (Default value of CaBuffer0) as well
	FROM i=0 TO NANN-1 {
		ca[i] = cai
	}

       	ipump 	= 0
        pump 	= totpump
        pumpca 	= (1e-18)*pump*cao*k4/k3

        FROM i=0 TO NANN-1 {
               	ca[i] = cai
		CaBuffer[i] =(totbuf*ca[i])/(k2buf/k1buf+ca[i])
		Buffer[i] = totbuf - CaBuffer[i]
	}
}

LOCAL frat[NANN] 	: gets extra cm when multiplied by diam

PROCEDURE coord() {
	LOCAL r, dr2
	: cylindrical coordinate system  with constant annuli thickness to
	: center of cell. Note however that the first annulus is half thickness
	: so that the concentration is second order correct spatially at
	: the membrane or exact edge of the cell.
	: note ca[0] is at edge of cell
	:      ca[NANN-1] is at center of cell
	r = 1/2					:starts at edge (half diam)
	dr2 = r/(NANN-1)/2			:half thickness of annulus
	vol[0] = 0
	frat[0] = 2*r
	FROM i=0 TO NANN-2 {
		vol[i] = vol[i] + PI*(r-dr2/2)*2*dr2	:interior half
		r = r - dr2
		frat[i+1] = 2*PI*r/(2*dr2)	:exterior edge of annulus
					: divided by distance between centers
		r = r - dr2
		vol[i+1] = PI*(r+dr2/2)*2*dr2	:outer half of annulus
	}
}

LOCAL dsq, dsqvol : can't define local variable in KINETIC block or use
		:  in COMPARTMENT
KINETIC state {
	COMPARTMENT i, diam*diam*vol[i]*1(um) {ca CaBuffer Buffer}
        COMPARTMENT (1.e10)*area {pump pumpca}
        COMPARTMENT (1.e15)*volo {cao}

	~ ca[0] << (-(ica-last_ipump)*PI*diam*frat[0]*1(um)/(2*FARADAY))

	FROM i=0 TO NANN-2 {
		~ ca[i] <-> ca[i+1] 	(DFree*frat[i+1]*1(um), DFree*frat[i+1]*1(um))
	}

	dsq = diam*diam*1(um)
	FROM i=0 TO NANN-1 {
		dsqvol = dsq*vol[i]
		~ ca[i] + Buffer[i] <-> CaBuffer[i] (k1buf*dsqvol,k2buf*dsqvol)
	}

        ~ca[0] + pump <-> pumpca 	((1.e-11)*k1*area, (1.e7)*k2*area)
        ~pumpca       <-> pump + cao 	((1.e7)*k3*area, (1.e-11)*k4*area)

        ipump = 2*FARADAY*(f_flux-b_flux)/area

	cai = ca[0]
}

COMMENT
At this time, conductances (and channel states and currents are
calculated at the midpoint of a dt interval.  Membrane potential and
concentrations are calculated at the edges of a dt interval.  With
secondorder=2 everything turns out to be second order correct.
ENDCOMMENT



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