Cerebellar Purkinje Cell: resurgent Na current and high frequency firing (Khaliq et al 2003)

 Download zip file   Auto-launch 
Help downloading and running models
Accession:48332
These mod files supplied by Dr Raman are for the below two references. ... we modeled action potential firing by simulating eight currents directly recorded from Purkinje cells in both wild-type and (mutant) med mice. Regular, high-frequency firing was slowed in med Purkinje neurons. In addition to disrupted sodium currents, med neurons had small but significant changes in potassium and leak currents. Simulations indicated that these modified non-sodium currents could not account for the reduced excitability of med cells but instead slightly facilitated spiking. The loss of NaV1.6-specific kinetics, however, slowed simulated spontaneous activity. Together, the data suggest that across a range of conditions, sodium currents with a resurgent component promote and accelerate firing. See papers for more and details.
Reference:
1 . Khaliq ZM, Gouwens NW, Raman IM (2003) The contribution of resurgent sodium current to high-frequency firing in Purkinje neurons: an experimental and modeling study. J Neurosci 23:4899-912 [PubMed]
2 . Raman IM, Bean BP (2001) Inactivation and recovery of sodium currents in cerebellar Purkinje neurons: evidence for two mechanisms. Biophys J 80:729-37 [PubMed]
Citations  Citation Browser
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): Cerebellum Purkinje GABA cell;
Channel(s): 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): Activity Patterns; Ion Channel Kinetics; Action Potentials;
Implementer(s): Raman, Indira M [i-raman at northwestern.edu]; Bean, Bruce [bruce_bean at hms.harvard.edu]; Gouwens, Nathan W [nathan_gouwens at hms.harvard.edu];
Search NeuronDB for information about:  Cerebellum Purkinje GABA cell; I Na,t; I K; I h; I K,Ca; I Sodium; I Calcium; I Potassium;
TITLE Rsg sodium channel
: Resurgent sodium channel (with blocking particle)
: with updated kinetic parameters from Raman and Bean  

NEURON {
  SUFFIX naRsg
  USEION na READ ena WRITE ina
  RANGE g, gbar
}

UNITS { 
	(mV) = (millivolt)
	(S) = (siemens)
}

PARAMETER {
	gbar = .015			(S/cm2)

	: kinetic parameters
	Con = 0.005			(/ms)					: closed -> inactivated transitions
	Coff = 0.5			(/ms)					: inactivated -> closed transitions
	Oon = .75			(/ms)					: open -> Ineg transition
	Ooff = 0.005		(/ms)					: Ineg -> open transition
	alpha = 150			(/ms)					: activation
	beta = 3			(/ms)					: deactivation
	gamma = 150			(/ms)					: opening
	delta = 40			(/ms)					: closing, greater than BEAN/KUO = 0.2
	epsilon = 1.75		(/ms)					: open -> Iplus for tau = 0.3 ms at +30 with x5
	zeta = 0.03			(/ms)					: Iplus -> open for tau = 25 ms at -30 with x6

	: Vdep
	x1 = 20				(mV)								: Vdep of activation (alpha)
	x2 = -20			(mV)								: Vdep of deactivation (beta)
	x3 = 1e12			(mV)								: Vdep of opening (gamma)
	x4 = -1e12			(mV)								: Vdep of closing (delta)
	x5 = 1e12			(mV)								: Vdep into Ipos (epsilon)
	x6 = -25			(mV)								: Vdep out of Ipos (zeta)
}

ASSIGNED {
	alfac   				: microscopic reversibility factors
	btfac				

	: rates
	f01  		(/ms)
	f02  		(/ms)
	f03 		(/ms)
	f04			(/ms)
	f0O 		(/ms)
	fip 		(/ms)
	f11 		(/ms)
	f12 		(/ms)
	f13 		(/ms)
	f14 		(/ms)
	f1n 		(/ms)
	fi1 		(/ms)
	fi2 		(/ms)
	fi3 		(/ms)
	fi4 		(/ms)
	fi5 		(/ms)
	fin 		(/ms)

	b01 		(/ms)
	b02 		(/ms)
	b03 		(/ms)
	b04		(/ms)
	b0O 		(/ms)
	bip 		(/ms)
	b11  		(/ms)
	b12 		(/ms)
	b13 		(/ms)
	b14 		(/ms)
	b1n 		(/ms)
	bi1 		(/ms)
	bi2 		(/ms)
	bi3 		(/ms)
	bi4 		(/ms)
	bi5 		(/ms)
	bin 		(/ms)
	
	v					(mV)
 	ena					(mV)
	ina 					(milliamp/cm2)
	g					(S/cm2)
}

STATE {
	C1 FROM 0 TO 1
	C2 FROM 0 TO 1
	C3 FROM 0 TO 1
	C4 FROM 0 TO 1
	C5 FROM 0 TO 1
	I1 FROM 0 TO 1
	I2 FROM 0 TO 1
	I3 FROM 0 TO 1
	I4 FROM 0 TO 1
	I5 FROM 0 TO 1
	O FROM 0 TO 1
	B FROM 0 TO 1
	I6 FROM 0 TO 1
}

BREAKPOINT {
 SOLVE activation METHOD sparse
 g = gbar * O
 ina = g * (v - ena)
}

INITIAL {
 rates(v)
 SOLVE seqinitial
}

KINETIC activation
{
	rates(v)
	~ C1 <-> C2					(f01,b01)
	~ C2 <-> C3					(f02,b02)
	~ C3 <-> C4					(f03,b03)
	~ C4 <-> C5					(f04,b04)
	~ C5 <-> O					(f0O,b0O)
	~ O <-> B					(fip,bip)
	~ O <-> I6					(fin,bin)
	~ I1 <-> I2					(f11,b11)
	~ I2 <-> I3					(f12,b12)
	~ I3 <-> I4					(f13,b13)
	~ I4 <-> I5					(f14,b14)
	~ I5 <-> I6					(f1n,b1n)
	~ C1 <-> I1					(fi1,bi1)
	~ C2 <-> I2					(fi2,bi2)
	~ C3 <-> I3					(fi3,bi3)
 	~ C4 <-> I4					(fi4,bi4)
 	~ C5 <-> I5					(fi5,bi5)

CONSERVE C1 + C2 + C3 + C4 + C5 + O + B + I1 + I2 + I3 + I4 + I5 + I6 = 1
}

LINEAR seqinitial { : sets initial equilibrium
 ~          I1*bi1 + C2*b01 - C1*(    fi1+f01) = 0
 ~ C1*f01 + I2*bi2 + C3*b02 - C2*(b01+fi2+f02) = 0
 ~ C2*f02 + I3*bi3 + C4*b03 - C3*(b02+fi3+f03) = 0
 ~ C3*f03 + I4*bi4 + C5*b04 - C4*(b03+fi4+f04) = 0
 ~ C4*f04 + I5*bi5 + O*b0O - C5*(b04+fi5+f0O) = 0
 ~ C5*f0O + B*bip + I6*bin - O*(b0O+fip+fin) = 0
 ~ O*fip + B*bip = 0

 ~          C1*fi1 + I2*b11 - I1*(    bi1+f11) = 0
 ~ I1*f11 + C2*fi2 + I3*b12 - I2*(b11+bi2+f12) = 0
 ~ I2*f12 + C3*fi3 + I4*bi3 - I3*(b12+bi3+f13) = 0
 ~ I3*f13 + C4*fi4 + I5*b14 - I4*(b13+bi4+f14) = 0
 ~ I4*f14 + C5*fi5 + I6*b1n - I5*(b14+bi5+f1n) = 0
 
 ~ C1 + C2 + C3 + C4 + C5 + O + B + I1 + I2 + I3 + I4 + I5 + I6 = 1
}

PROCEDURE rates(v(mV) )
{
 alfac = (Oon/Con)^(1/4)
 btfac = (Ooff/Coff)^(1/4) 
 f01 = 4 * alpha * exp(v/x1)
 f02 = 3 * alpha * exp(v/x1)
 f03 = 2 * alpha * exp(v/x1)
 f04 = 1 * alpha * exp(v/x1)
 f0O = gamma * exp(v/x3)
 fip = epsilon * exp(v/x5)
 f11 = 4 * alpha * alfac * exp(v/x1)
 f12 = 3 * alpha * alfac * exp(v/x1)
 f13 = 2 * alpha * alfac * exp(v/x1)
 f14 = 1 * alpha * alfac * exp(v/x1)
 f1n = gamma * exp(v/x3)
 fi1 = Con
 fi2 = Con * alfac
 fi3 = Con * alfac^2
 fi4 = Con * alfac^3
 fi5 = Con * alfac^4
 fin = Oon

 b01 = 1 * beta * exp(v/x2)
 b02 = 2 * beta * exp(v/x2)
 b03 = 3 * beta * exp(v/x2)
 b04 = 4 * beta * exp(v/x2)
 b0O = delta * exp(v/x4)
 bip = zeta * exp(v/x6)
 b11 = 1 * beta * btfac * exp(v/x2)
 b12 = 2 * beta * btfac * exp(v/x2)
 b13 = 3 * beta * btfac * exp(v/x2)
 b14 = 4 * beta * btfac * exp(v/x2)
 b1n = delta * exp(v/x4)
 bi1 = Coff
 bi2 = Coff * btfac
 bi3 = Coff * btfac^2
 bi4 = Coff * btfac^3
 bi5 = Coff * btfac^4
 bin = Ooff
}