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KCC2.mod
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:------------------------------------------------------------------------------
TITLE Model of KCC2 regulation
:------------------------------------------------------------------------------
NEURON {
SUFFIX KCC2
:USEION ca READ ica, cao WRITE cai
USEION ca READ cai
USEION mkcc2 WRITE mkcc2i VALENCE 1
RANGE A_M, B_M
RANGE R_M, R_MP
RANGE R_K, R_P, V_K, V_P, H_K, H_P, B_K, B_P
RANGE kin_active, kin_inactive, cyt, memb, membp, v_K, v_P
}
UNITS {
(mV) = (millivolt)
(um) = (micron)
(mA) = (milliamp)
(M) = (1/liter)
(mM) = (milliM)
(J) = (joule)
(S) = (siemens)
F = (faraday) (coulombs)
R = (k-mole) (joule/degC)
PI = (pi) (1)
}
PARAMETER {
A_M = 0.2533 (/s) < 0, 1e9 > : rate of transfer from cytosolic to membrane-bound KCC2
B_M = 1.4776 (/s) < 0, 1e9 > : rate of transfer from membrane-bound to cytosolic KCC2
R_M = 1 (/s) < 0, 1e9 > : KCC2 phosphorylation coefficient
R_MP = 0.0646 (/s) < 0, 1e9 > : KCC2 dephosphorylation coefficient
R_K = 2.37e-3 (mM) < 0, 1e9 > : concent. of Ca2+ at which kinase activation rate is half max
R_P = 7.943e-4 (mM) < 0, 1e9 > : concent. of Ca2+ at which phosphotase activation rate is half max
V_K = 390 (/s) < 0, 1e9 > : maximum rate of kinase activation
V_P = 48.925 (/s) < 0, 1e9 > : maximum rate of phosphotase activation
H_K = 1.5 (1) < 0, 1e9 > : Hill coefficient for kinase activation equation
H_P = 2.9 (1) < 0, 1e9 > : Hill coefficient for phosphotase activation equation
B_K = 32.1 (/s) < 0, 1e9 > : rate of kinase inactivation
B_P = 10 (/s) < 0, 1e9 > : rate of phosphotase inactivation
gcal = 7e-3 (mho/cm2)
}
ASSIGNED {
v (mV) : membrane voltage
diam (um) : compartment diameter
mkcc2i (mM) : concentration of membrane-bound KCC2
cai (mM) : calcium concentration
ica (mA/cm2): calcium concentration
v_K (/s) : rate of kinase activation
v_P (/s) : rate of phosphotase activation
celsius (degC) : temperature
cao (mM) : extracellular calcium concentration
}
STATE {
kin_active
kin_inactive
phos_active
phos_inactive
cyt
memb
membp
}
INITIAL {
kin_active = 0.1050423664
kin_inactive = 0.8949576336
phos_active = 0.0222547827
phos_inactive = 0.9777452173
cyt = 0.8000684487
memb = 0.1371530442
membp = 0.0627785071
}
BREAKPOINT {
SOLVE states METHOD cnexp
}
DERIVATIVE states {
enzymes(cai)
cyt' = (1e-3)*(B_M*memb - A_M*cyt)
memb' = (1e-3)*(A_M*cyt - (B_M + R_MP*kin_active)*memb + R_M*phos_active*membp)
membp' = (1e-3)*(-R_M*phos_active*membp + R_MP*kin_active*memb)
kin_inactive = 1 - kin_active
phos_inactive = 1 - phos_active
:kin_inactive' = (1e-3)*(-kin_inactive*v_K + B_K*kin_active)
:phos_inactive' = (1e-3)*(-phos_inactive*v_P + B_P*phos_active)
kin_active' = (1e-3)*(kin_inactive*v_K - B_K*kin_active)
phos_active' = (1e-3)*(phos_inactive*v_P - B_P*phos_active)
if (memb + membp > 0) {
mkcc2i = (memb + membp)*1(mM)
}
else {
mkcc2i = 0
}
}
PROCEDURE enzymes (Caint (mM)) {
v_K = (V_K*((Caint/1(mM))^H_K))/((R_K/1(mM))^H_K + (Caint/1(mM))^H_K)
v_P = (V_P*((Caint/1(mM))^H_P))/((R_P/1(mM))^H_P + (Caint/1(mM))^H_P)
}