TITLE Voltage-dependent kinetic model of NMDA receptor
COMMENT
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Kinetic model of NMDA receptors
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16-state gating model:
Clarke and Johnson, 2008
RA2d1 RA2d1Mg
| - RA2f - - RA2fMg - |
R -- RA -- RA2 =< >= RA2O -- RA2OMg =< >= RA2Mg -- RAMg -- RMg
| - RA2s - - RA2sMg - |
RA2d2 RA2d2Mg
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Based on voltage-clamp recordings of NMDA receptor-mediated currents in
nucleated patches of rat layer II/III cortical pyramidal cells
in the occipital cortex (Clarke and Johnson, 2008),
this model was originally fitted with Matlab to experimental recordings in
order to obtain the optimal values for the parameters.
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Release process modeled with an internal alpha function in order to make it compatible
with NetCon onbject, and therefore does not require an external release mechanism.
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Unit of g is in uS to make the synaptic weights compatible with
NEURON's internal methods of modeling synapses (e.x. exp2syn)
for more information see the chapter 10 of the neuron book
This mod file is written by Keivan Moradi 2012
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ENDCOMMENT
INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}
NEURON {
POINT_PROCESS NMDA16
USEION na READ nao
RANGE T_max, T, tau, tRel, Erev, synon
RANGE R,RA,RA2,RA2d1,RA2d2,RA2f,RA2s,O,OMg,RMg,RAMg,RA2Mg,RA2d1Mg,RA2d2Mg,RA2fMg,RA2sMg
RANGE g, kd1F, kd1B, kd2F, kd2B, csi
GLOBAL Kcs, kP, kNo, kNi, kMgF, kMgB, ksF, ksB, kfF, kfB
NONSPECIFIC_CURRENT i
THREADSAFE
}
UNITS {
(nA) = (nanoamp)
(mV) = (millivolt)
(pS) = (picosiemens)
(uS) = (microsiemens)
(umho) = (micromho)
(mM) = (milli/liter)
(uM) = (micro/liter)
}
PARAMETER {
Erev = 0 (mV) : reversal potential
gmax = 50 (pS) : maximal conductance Johnson & Ascher, 1990
Mg = 1 (mM) : external magnesium concentration
: alpha function formalism
tau = .3 (ms) <1e-9,1e9>
T_max = 1.5 (mM) : maximum concentration of neurotransmitter
: Rates
kon = 2.83 (/ms /mM)
koff = 38.1e-3 (/ms)
: voltage dependent rates
ksF0 = 48e-3 (/ms)
ksB0 = 230e-3 (/ms)
kfF0 = 2836e-3 (/ms)
kfB0 = 175e-3 (/ms)
Vdep = 175 (mV) : sensitivity to membrane voltage
V0 = -100 (mV) : the membrane voltage with no voltage-dependetn component
: kd1F, kd1B, kd2F and kd2B should be found with optimization method since
: NMDAR in different regions of the brain have different time course
kd1F = 1e-3 (/ms)
kd1B = 1e-3 (/ms)
kd2F = 1e-3 (/ms)
kd2B = 1e-3 (/ms)
: Parameters that control the Mg block as in Antonov99
Kna = 34.4 (mM)
Kcs0 = 0.27 (mM)
a = -21 (mV)
kP0 = 1.10e3 (/ms /mM)
b = -55 (mV)
kNo0 = 1.10e2 (/ms)
c = 52.7 (mV)
kNi0 = 61.8e-3 (/ms)
d = -50 (mV)
csi = 148 (mM) : internal Cs++ concentration (125 mM CsCl + 23 mM CsOH)
: KMg0 = 101e-3 (mM)
: e = 26.9 (mV)
}
ASSIGNED {
v (mV) : postsynaptic voltage
i (nA) : current = g*(v - Erev)
g (uS) : conductance
T (mM) : neurotransmiter concentration in the cleft
tRel (ms) : spiking time of the presynaptic cell
synon : turns the synapse on or Off
w : weight of synapse
: voltage-dependnent rates
ksF (/ms)
ksB (/ms)
kfF (/ms)
kfB (/ms)
: Mg-block and -unblock rates
kMgF (/ms /mM)
kMgB (/ms)
: Parameters that Mg-block and -unblock rates or the so called apparent-block and -unblock
Kcs (mM)
kP (/ms /mM)
kNo (/ms)
kNi (/ms)
nao (mM) : Na+ concentration outside the cell, its value should be assigned in the hoc section
: KMg (mM)
}
STATE {
: Channel states (all fractions)
R
RA
RA2
RA2d1
RA2d2
RA2f
RA2s
O
OMg
RMg
RAMg
RA2Mg
RA2d1Mg
RA2d2Mg
RA2fMg
RA2sMg
}
INITIAL {
T = 0
synon = 0
tRel = 0
R = 1
rates(v,t)
}
BREAKPOINT {
SOLVE kstates METHOD sparse
g = w * gmax * O
i = g * (v - Erev)
}
KINETIC kstates {
rates(v,t)
: RA2d1 RA2d1Mg
: | - RA2f - - RA2fMg - |
: R -- RA -- RA2 =< >= O -- OMg =< >= RA2Mg -- RAMg -- RMg
: | - RA2s - - RA2sMg - |
: RA2d2 RA2d2Mg
~ R <-> RA ((2*kon*T),koff)
~ RA <-> RA2 ((kon*T),(2*koff))
~ RA2 <-> RA2d1 (kd1F,kd1B)
~ RA2 <-> RA2d2 (kd2F,kd2B)
~ RA2 <-> RA2f (kfF,kfB)
~ RA2 <-> RA2s (ksF,ksB)
~ RA2f <-> O (ksF,ksB)
~ RA2s <-> O (kfF,kfB)
~ O <-> OMg ((kMgF*Mg),kMgB)
~ OMg <-> RA2fMg (ksB,ksF)
~ OMg <-> RA2sMg (kfB,kfF)
~ RA2fMg <-> RA2Mg (kfB,kfF)
~ RA2sMg <-> RA2Mg (ksB,ksF)
~ RA2Mg <-> RA2d1Mg (kd1B,kd1F)
~ RA2Mg <-> RA2d2Mg (kd2B,kd2F)
~ RA2Mg <-> RAMg ((2*koff),(kon*T))
~ RAMg <-> RMg (koff,(2*kon*T))
CONSERVE R+RA+RA2+RA2d1+RA2d2+RA2f+RA2s+O+OMg+RMg+RAMg+RA2Mg+RA2d1Mg+RA2d2Mg+RA2fMg+RA2sMg = 1
}
NET_RECEIVE(weight) {
if (flag == 0) {
tRel = t : resets the alpha function
synon = 1 : turns the synapse on.
: The alpha function does not require to turn off the synase
w = weight
}
}
PROCEDURE rates(v (mV), t(ms)) {
T = T_max * (t - tRel) / tau * exp(1 - (t - tRel) / tau) * synon
Kcs = Kcs0 * exp(v/a)
kP = kP0 * exp(v/b)
kNo = kNo0 * exp(v/c)
kNi = kNi0 * exp(v/d)
kMgF = kP / ((1 + nao/Kna) * (1 + nao/Kna + csi/Kcs))
kMgB = kNo / (1 + nao/Kna)^2 + kNi
: KMg = KMg0 * exp(v/e)
ksF = ksF0 * exp((v - V0) / Vdep)
ksB = ksB0 * exp((v - V0) / Vdep * (-1))
kfF = kfF0 * exp((v - V0) / Vdep)
kfB = kfB0 * exp((v - V0) / Vdep * (-1))
}
