COMMENT
Chloride accumulation and diffusion with decay (time constant tau) to resting level cli0.
The decay approximates a reversible chloride pump with first order kinetics.
To eliminate the chloride pump, just use this hoc statement
To make the time constant effectively "infinite".
tau and the resting level are both RANGE variables
Diffusion model is modified from Ca diffusion model in Hines & Carnevale:
Expanding NEURON with NMODL, Neural Computation 12: 839-851, 2000 (Example 8)
ENDCOMMENT
NEURON {
SUFFIX cldif_CA3
USEION cl READ icl WRITE cli VALENCE -1
USEION hco3 READ hco3i, hco3o VALENCE -1
GLOBAL vrat :vrat must be GLOBAL
RANGE tau, cli0, clo0, egaba, delta_egaba, init_egaba, ehco3_help, ecl_help
}
DEFINE Nannuli 4
UNITS {
(molar) = (1/liter)
(mM) = (millimolar)
(um) = (micron)
(mA) = (milliamp)
(mV) = (millivolt)
FARADAY = (faraday) (10000 coulomb)
PI = (pi) (1)
F = (faraday) (coulombs)
R = (k-mole) (joule/degC)
}
PARAMETER {
DCl = 2 (um2/ms) : Kuner & Augustine, Neuron 27: 447
tau = 174000 (ms) : According to our results
cli0 = 8 (mM)
clo0 = 133.5 (mM)
hco3i0 = 16 (mM)
hco3o0 = 26 (mM)
P_help = 0.18
celsius = 37 (degC)
}
ASSIGNED {
diam (um)
icl (mA/cm2)
cli (mM)
hco3i (mM)
hco3o (mM)
vrat[Nannuli] : numeric value of vrat[i] equals the volume
: of annulus i of a 1um diameter cylinder
: multiply by diam^2 to get volume per um length
egaba (mV)
ehco3_help (mV)
ecl_help (mV)
init_egaba (mV)
delta_egaba (mV)
}
STATE {
: cl[0] is equivalent to cli
: cl[] are very small, so specify absolute tolerance
cl[Nannuli] (mM) <1e-10>
}
BREAKPOINT {
SOLVE state METHOD sparse
ecl_help = log(cli/clo0)*(1000)*(celsius + 273.15)*R/F
egaba = P_help*ehco3_help + (1-P_help)*ecl_help
delta_egaba = egaba - init_egaba
}
LOCAL factors_done
INITIAL {
if (factors_done == 0) { : flag becomes 1 in the first segment
factors_done = 1 : all subsequent segments will have
factors() : vrat = 0 unless vrat is GLOBAL
}
cli = cli0
hco3i = hco3i0
hco3o = hco3o0
FROM i=0 TO Nannuli-1 {
cl[i] = cli
}
ehco3_help = log(hco3i/hco3o)*(1000)*(celsius + 273.15)*R/F
ecl_help = log(cli/clo0)*(1000)*(celsius + 273.15)*R/F
egaba = P_help*ehco3_help + (1-P_help)*ecl_help
init_egaba = egaba
delta_egaba = egaba - init_egaba
}
LOCAL frat[Nannuli] : scales the rate constants for model geometry
PROCEDURE factors() {
LOCAL r, dr2
r = 1/2 : starts at edge (half diam), diam = 1, length = 1
dr2 = r/(Nannuli-1)/2 : full thickness of outermost annulus,
: half thickness of all other annuli
vrat[0] = 0
frat[0] = 2*r : = diam
FROM i=0 TO Nannuli-2 {
vrat[i] = vrat[i] + PI*(r-dr2/2)*2*dr2 : interior half
r = r - dr2
frat[i+1] = 2*PI*r/(2*dr2) : outer radius of annulus Ai+1/delta_r=2PI*r*1/delta_r
: div by distance between centers
r = r - dr2
vrat[i+1] = PI*(r+dr2/2)*2*dr2 : outer half of annulus
}
}
KINETIC state {
COMPARTMENT i, diam*diam*vrat[i] {cl}
LONGITUDINAL_DIFFUSION i, DCl*diam*diam*vrat[i] {cl}
~ cl[0] << ((icl*PI*diam/FARADAY) + (diam*diam*vrat[0]*(cli0 - cl[0])/tau)) : icl is Cl- influx
FROM i=0 TO Nannuli-2 {
~ cl[i] <-> cl[i+1] (DCl*frat[i+1], DCl*frat[i+1])
}
cli = cl[0]
}