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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Rates modified for near physiological temperatures with Q10 values from
O.Cais et al 2008, Mg unbinding from Vargas-Caballero 2003, opening and
closing from Lester and Jahr 1992.
Tiago Branco 2010
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ENDCOMMENT
INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}
NEURON {
POINT_PROCESS NMDA_Mg_T
POINTER C
RANGE U, Cl, D1, D2, O, UMg, ClMg, D1Mg, D2Mg, OMg
RANGE g, gmax, rb, rmb, rmu, rbMg,rmc1b,rmc1u,rmc2b,rmc2u
GLOBAL Erev, 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 vmin, vmax, valence, memb_fraction
NONSPECIFIC_CURRENT i
}
UNITS {
(nA) = (nanoamp)
(mV) = (millivolt)
(pS) = (picosiemens)
(umho) = (micromho)
(mM) = (milli/liter)
(uM) = (micro/liter)
}
PARAMETER {
Erev = 5 (mV) : reversal potential
gmax = 500 (pS) : maximal conductance
mg = 1 (mM) : external magnesium concentration
vmin = -120 (mV)
vmax = 100 (mV)
valence = -2 : parameters of voltage-dependent Mg block
memb_fraction = 0.8
: Rates
Rb = 10e-3 (/uM /ms) : binding
Ru = 0.02016 (/ms) : unbinding
Ro = 46.5e-3 (/ms) : opening
Rc = 91.6e-3 (/ms) : closing
Rd1 = 0.02266 (/ms) : fast desensitisation
Rr1 = 0.00736 (/ms) : fast resensitisation
Rd2 = 0.004429 (/ms) : slow desensitisation
Rr2 = 0.0023 (/ms) : slow resensitisation
Rmb = 0.05e-3 (/uM /ms) : Mg binding Open
Rmu = 12800e-3 (/ms) : Mg unbinding Open
Rmc1b = 0.00005e-3 (/uM /ms) : Mg binding Closed
Rmc1u = 0.06 (/ms) : Mg unbinding Closed
Rmc2b = 0.00005e-3 (/uM /ms) : Mg binding Closed2
Rmc2u = 0.06 (/ms) : Mg unbinding Closed2
Rmd1b = 0.00005e-3 (/uM /ms) : Mg binding Desens1
Rmd1u = 0.06 (/ms) : Mg unbinding Desens1
Rmd2b = 0.00005e-3 (/uM /ms) : Mg binding Desens2
Rmd2u = 0.06 (/ms) : Mg unbinding Desens2
RbMg = 10e-3 (/uM /ms) : binding with Mg
RuMg = 0.06156 (/ms) : unbinding with Mg
RoMg = 46.5e-3 (/ms) : opening with Mg
RcMg = 91.6e-3 (/ms) : closing with Mg
Rd1Mg = 0.02163 (/ms) : fast desensitisation with Mg
Rr1Mg = 0.004002 (/ms) : fast resensitisation with Mg
Rd2Mg = 0.002678 (/ms) : slow desensitisation with Mg
Rr2Mg = 0.001932 (/ms) : slow resensitisation with Mg
}
ASSIGNED {
v (mV) : postsynaptic voltage
i (nA) : current = g*(v - Erev)
g (pS) : conductance
C (mM) : pointer to glutamate concentration
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 {
U = 1
}
BREAKPOINT {
SOLVE kstates METHOD sparse
g = gmax * O
i = (1e-6) * g * (v - Erev)
}
KINETIC kstates {
rb = Rb * (1e3) * C
rbMg = RbMg * (1e3) * C
rmb = Rmb * mg * (1e3) * exp((v-40) * valence * memb_fraction /25)
rmu = Rmu * exp((-1)*(v-40) * valence * (1-memb_fraction) /25)
rmc1b = Rmc1b * mg * (1e3) * exp((v-40) * valence * memb_fraction /25)
rmc1u = Rmc1u * exp((-1)*(v-40) * valence * (1-memb_fraction) /25)
rmc2b = Rmc2b * mg * (1e3) * exp((v-40) * valence * memb_fraction /25)
rmc2u = Rmc2u * exp((-1)*(v-40) * valence * (1-memb_fraction) /25)
rmd1b = Rmd1b * mg * (1e3) * exp((v-40) * valence * memb_fraction /25)
rmd1u = Rmd1u * exp((-1)*(v-40) * valence * (1-memb_fraction) /25)
rmd2b = Rmd2b * mg * (1e3) * exp((v-40) * valence * memb_fraction /25)
rmd2u = Rmd2u * exp((-1)*(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
}