TITLE kinetic NMDA receptor model
COMMENT
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Kinetic model of NMDA receptors
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10-state gating model:
Kampa et al. (2004) J Physiol
U -- Cl -- O
\ | \ \
\ | \ \
UMg -- ClMg - OMg
| |
D1 |
| \ |
| \ |
D2 \|
\ D1Mg
\ |
\ |
D2Mg
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Based on voltage-clamp recordings of NMDA receptor-mediated currents in
nucleated patches of rat neocortical layer 5 pyramidal neurons (Kampa 2004),
this model was fit with AxoGraph directly to experimental recordings in
order to obtain the optimal values for the parameters.
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This mod file does not include mechanisms for the release and time course
of transmitter; it should to be used in conjunction with a sepearate mechanism
to describe the release of transmitter and tiemcourse of the concentration
of transmitter in the synaptic cleft (to be connected to pointer C here).
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See details of NEURON kinetic models in:
Destexhe, A., Mainen, Z.F. and Sejnowski, T.J. Kinetic models of
synaptic transmission. In: Methods in Neuronal Modeling (2nd edition;
edited by Koch, C. and Segev, I.), MIT press, Cambridge, 1996.
Written by Bjoern Kampa in 2004
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These modifications are made by Keivan Moradi 2007 to 2012:
- 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.
- Unit of g changed from pS to uS to make the synaptic weights compatible with
NEURON's internal methods of modeling synapses (e.x. exp2syn)
- gmax is set to 50 Johnson & Ascher, 1990
- rate constant units changed from (/uM /ms) to (/mM /ms) to remove the annoying coefficients
- valence of Mg is +2. Why it is -2 here?
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ENDCOMMENT
INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}
NEURON {
POINT_PROCESS NMDA10_1
RANGE T_max, T, tau, tRel, Erev, synon
RANGE U, Cl, D1, D2, O, UMg, ClMg, D1Mg, D2Mg, OMg
RANGE g, gmax, rb, rmb, rmu, rbMg,rmc1b,rmc1u,rmc2b,rmc2u
GLOBAL mg, Rb, Ru, Rd1, Rr1, Rd2, Rr2, Ro, Rc, Rmb, Rmu
GLOBAL RbMg, RuMg, Rd1Mg, Rr1Mg, Rd2Mg, Rr2Mg, RoMg, RcMg
GLOBAL Rmd1b,Rmd1u,Rmd2b,Rmd2u,rmd1b,rmd1u,rmd2b,rmd2u
GLOBAL Rmc1b,Rmc1u,Rmc2b,Rmc2u
GLOBAL valence, memb_fraction
NONSPECIFIC_CURRENT i
}
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
mg = 1 (mM) : external magnesium concentration
valence = -2 : parameters of voltage-dependent Mg block
memb_fraction = 0.8
: alpha function formalism
tau = .3 (ms) <1e-9,1e9>
T_max = 1.5 (mM) : maximum concentration of neurotransmitter
: Rates
Rb = 10 (/mM /ms) : binding
Ru = 5.6e-3 (/ms) : unbinding
Ro = 10e-3 (/ms) : opening
Rc = 273e-3 (/ms) : closing
Rd1 = 2.2e-3 (/ms) : fast desensitisation
Rr1 = 1.6e-3 (/ms) : fast resensitisation
Rd2 = 0.43e-3 (/ms) : slow desensitisation
Rr2 = 0.5e-3 (/ms) : slow resensitisation
Rmb = 0.05 (/mM /ms) : Mg binding Open
Rmu = 12800e-3 (/ms) : Mg unbinding Open
Rmc1b = 0.00005 (/mM /ms) : Mg binding Closed
Rmc1u = 2.438312e-3 (/ms) : Mg unbinding Closed
Rmc2b = 0.00005 (/mM /ms) : Mg binding Closed2
Rmc2u = 5.041915e-3 (/ms) : Mg unbinding Closed2
Rmd1b = 0.00005 (/mM /ms) : Mg binding Desens1
Rmd1u = 2.98874e-3 (/ms) : Mg unbinding Desens1
Rmd2b = 0.00005 (/mM /ms) : Mg binding Desens2
Rmd2u = 2.953408e-3 (/ms) : Mg unbinding Desens2
RbMg = 10 (/mM /ms) : binding with Mg
RuMg = 17.1e-3 (/ms) : unbinding with Mg
RoMg = 10e-3 (/ms) : opening with Mg
RcMg = 548e-3 (/ms) : closing with Mg
Rd1Mg = 2.1e-3 (/ms) : fast desensitisation with Mg
Rr1Mg = 0.87e-3 (/ms) : fast resensitisation with Mg
Rd2Mg = 0.26e-3 (/ms) : slow desensitisation with Mg
Rr2Mg = 0.42e-3 (/ms) : slow resensitisation with Mg
}
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
rb (/ms) : binding, [glu] dependent
rmb (/ms) : blocking V and [Mg] dependent
rmu (/ms) : unblocking V and [Mg] dependent
rbMg (/ms) : binding, [glu] dependent
rmc1b (/ms) : blocking V and [Mg] dependent
rmc1u (/ms) : unblocking V and [Mg] dependent
rmc2b (/ms) : blocking V and [Mg] dependent
rmc2u (/ms) : unblocking V and [Mg] dependent
rmd1b (/ms) : blocking V and [Mg] dependent
rmd1u (/ms) : unblocking V and [Mg] dependent
rmd2b (/ms) : blocking V and [Mg] dependent
rmd2u (/ms) : unblocking V and [Mg] dependent
}
STATE {
: Channel states (all fractions)
U : unbound
Cl : closed
D1 : desensitised 1
D2 : desensitised 2
O : open
UMg : unbound with Mg
ClMg : closed with Mg
D1Mg : desensitised 1 with Mg
D2Mg : desensitised 2 with Mg
OMg : open with Mg
}
INITIAL {
T = 0
synon = 0
tRel = 0
U = 1
}
BREAKPOINT {
SOLVE kstates METHOD sparse
g = w * gmax * O
i = g * (v - Erev)
}
KINETIC kstates {
release(t)
rb = Rb * T
rbMg = RbMg * T
rmb = Rmb * mg * exp((1 (/mV) * v-40) * valence * memb_fraction /25)
rmu = Rmu * exp((-1 (/mV))*(v-40) * valence * (1-memb_fraction) /25)
rmc1b = Rmc1b * mg * exp((1 (/mV) * v-40) * valence * memb_fraction /25)
rmc1u = Rmc1u * exp((-1 (/mV))*(v-40) * valence * (1-memb_fraction) /25)
rmc2b = Rmc2b * mg * exp((1 (/mV) * v-40) * valence * memb_fraction /25)
rmc2u = Rmc2u * exp((-1 (/mV))*(v-40) * valence * (1-memb_fraction) /25)
rmd1b = Rmd1b * mg * exp((1 (/mV) * v-40) * valence * memb_fraction /25)
rmd1u = Rmd1u * exp((-1 (/mV))*(v-40) * valence * (1-memb_fraction) /25)
rmd2b = Rmd2b * mg * exp((1 (/mV) * v-40) * valence * memb_fraction /25)
rmd2u = Rmd2u * exp((-1 (/mV))*(v-40) * valence * (1-memb_fraction) /25)
~ U <-> Cl (rb,Ru)
~ Cl <-> O (Ro,Rc)
~ Cl <-> D1 (Rd1,Rr1)
~ D1 <-> D2 (Rd2,Rr2)
~ O <-> OMg (rmb,rmu)
~ UMg <-> ClMg (rbMg,RuMg)
~ ClMg <-> OMg (RoMg,RcMg)
~ ClMg <-> D1Mg (Rd1Mg,Rr1Mg)
~ D1Mg <-> D2Mg (Rd2Mg,Rr2Mg)
~ U <-> UMg (rmc1b,rmc1u)
~ Cl <-> ClMg (rmc2b,rmc2u)
~ D1 <-> D1Mg (rmd1b,rmd1u)
~ D2 <-> D2Mg (rmd2b,rmd2u)
CONSERVE U+Cl+D1+D2+O+UMg+ClMg+D1Mg+D2Mg+OMg = 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 release(t(ms)) {
T = T_max * (t - tRel) / tau * exp(1 - (t - tRel) / tau) * synon
}