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,vshift,f04,ina,epsilon,zeta,x1,x2,alpha
RANGE vshifta,vshifti,vshiftk
: THREADSAFE
}
UNITS {
(mV) = (millivolt)
(S) = (siemens)
}
CONSTANT {
q10 = 2.7
}
PARAMETER {
gbar = .015 (S/cm2)
: ena= 65 (mV)
: 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,set to 0 to eliminate the persistent component
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)
vshifta = 0 (mV) : steady state activation curve
vshifti = 0 (mV) : steady state inactivation curve
vshiftk = 0
}
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)
qt
}
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
Ca FROM 0 TO 1
Ia FROM 0 TO 1
}
BREAKPOINT {
SOLVE activation METHOD sparse
g = gbar * O
ina = g * (v - ena)
}
INITIAL {
qt = q10^((celsius-22 (degC))/10 (degC))
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)
Ca = C1 + C2 + C3 + C4 + C5
Ia = I1 + I2 + I3 + I4 + I5
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)) * qt
f02 = 3 * alpha * exp((v)/(x1)) * qt
f03 = 2 * alpha * exp((v)/(x1)) * qt
f04 = 1 * alpha * exp((v)/(x1)) * qt
f0O = gamma * qt : * exp(v/x3) - since x3 is infinity
fip = epsilon * qt : * exp(v/x5)
f11 = 4 * alpha * alfac * exp((v+vshifti)/x1) * qt
f12 = 3 * alpha * alfac * exp((v+vshifti)/x1) * qt
f13 = 2 * alpha * alfac * exp((v+vshifti)/x1) * qt
f14 = 1 * alpha * alfac * exp((v+vshifti)/x1) * qt
f1n = gamma * qt : * exp(v/x3) dito
fi1 = Con * qt
fi2 = Con * alfac * qt
fi3 = Con * alfac^2 * qt
fi4 = Con * alfac^3 * qt
fi5 = Con * alfac^4 * qt
fin = Oon * qt
b01 = 1 * beta * exp((v+vshifta)/(x2+vshiftk)) * qt
b02 = 2 * beta * exp((v+vshifta)/(x2+vshiftk)) * qt
b03 = 3 * beta * exp((v+vshifta)/(x2+vshiftk)) * qt
b04 = 4 * beta * exp((v+vshifta)/(x2+vshiftk)) * qt
b0O = delta * qt : * exp(v/x4)
bip = zeta * exp(v/x6) * qt
b11 = 1 * beta * btfac * exp((v+vshifti)/x2) * qt
b12 = 2 * beta * btfac * exp((v+vshifti)/x2) * qt
b13 = 3 * beta * btfac * exp((v+vshifti)/x2) * qt
b14 = 4 * beta * btfac * exp((v+vshifti)/x2) * qt
b1n = delta * qt : * exp(v/x4)
bi1 = Coff * qt
bi2 = Coff * btfac * qt
bi3 = Coff * btfac^2 * qt
bi4 = Coff * btfac^3 * qt
bi5 = Coff * btfac^4 * qt
bin = Ooff * qt
}