TITLE kinetic NMDA receptor model COMMENT ----------------------------------------------------------------------------- Kinetic model of NMDA receptors =============================== 10-state gating model: Kampa et al. (2004) J Physiol U -- Cl -- O \ | \ \ \ | \ \ UMg -- ClMg - OMg | | D1 | | \ | D2 \ | \ D1Mg \ | D2Mg ----------------------------------------------------------------------------- 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. ----------------------------------------------------------------------------- This mod file does not include mechanisms for the release and time course of transmitter; it should to be used in conjunction with a separate mechanism to describe the release of transmitter and timecourse of the concentration of transmitter in the synaptic cleft (to be connected to pointer XMTR here). ----------------------------------------------------------------------------- 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 Lightly modified, Paul Manis 2010. Note that data were taken at 23 deg C Q10 was taken from native receptors: Korinek M, Sedlacek M, Cais O, Dittert I, Vyklicky L Jr. Temperature dependence of N-methyl-D-aspartate receptor channels and N-methyl-D-aspartate receptor excitatory postsynaptic currents. Neuroscience. 2010 Feb 3;165(3):736-48. Epub 2009 Oct 31. PubMed PMID: 19883737. ----------------------------------------------------------------------------- ENDCOMMENT INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)} NEURON { THREADSAFE POINT_PROCESS NMDA_Kampa POINTER XMTR RANGE U, Cl, D1, D2, Open, MaxOpen, UMg, ClMg, D1Mg, D2Mg, OMg RANGE g, gmax, vshift, Erev, 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 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 vshift = 0.0 (mV) Q10 = 2.0 : temperature sensitivity (see above) : Maximum open probability with Mode=0 (no rectification). : This is determined empirically by holding XMTR at a large : value and v=40mV for 100 timesteps and measuring the : maximum value of Open. MaxOpen = 0.01988893957 (1) : Rates Rb = 10e-3 (/uM /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 Rd1 = 0.1 (/ms) : fast desensitisation Rr1 = 1.6e-3 (/ms) : fast resensitisation : Rd2 = 0.43e-3 (/ms) : slow desensitisation Rd2 = 1e-4 (/ms) : slow desensitisation Rr2 = 0.5e-3 (/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 = 2.438312e-3 (/ms) : Mg unbinding Closed Rmc2b = 0.00005e-3 (/uM /ms) : Mg binding Closed2 Rmc2u = 5.041915e-3 (/ms) : Mg unbinding Closed2 Rmd1b = 0.00005e-3 (/uM /ms) : Mg binding Desens1 Rmd1u = 2.98874e-3 (/ms) : Mg unbinding Desens1 Rmd2b = 0.00005e-3 (/uM /ms) : Mg binding Desens2 Rmd2u = 2.953408e-3 (/ms) : Mg unbinding Desens2 RbMg = 10e-3 (/uM /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 (pS) : conductance XMTR (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 qfac : Q10 celsius (degC) } STATE { : Channel states (all fractions) U : unbound Cl : closed D1 : desensitised 1 D2 : desensitised 2 Open : 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 qfac = Q10^((celsius-23)/10 (degC))} BREAKPOINT { SOLVE kstates METHOD sparse g = gmax * Open / MaxOpen i = (1e-6) * g * (v - Erev) } KINETIC kstates { rb = Rb * (1e3) * XMTR rbMg = RbMg * (1e3) * XMTR rmb = Rmb * mg * (1e3) * exp((v-40+vshift) * valence * memb_fraction /25 (mV)) rmu = Rmu * exp((-1)*(v-40+vshift) * valence * (1-memb_fraction) /25 (mV)) rmc1b = Rmc1b * mg * (1e3) * exp((v-40+vshift) * valence * memb_fraction /25 (mV)) rmc1u = Rmc1u * exp((-1)*(v-40+vshift) * valence * (1-memb_fraction) /25 (mV)) rmc2b = Rmc2b * mg * (1e3) * exp((v-40+vshift) * valence * memb_fraction /25 (mV)) rmc2u = Rmc2u * exp((-1)*(v-40+vshift) * valence * (1-memb_fraction) /25 (mV)) rmd1b = Rmd1b * mg * (1e3) * exp((v-40+vshift) * valence * memb_fraction /25 (mV)) rmd1u = Rmd1u * exp((-1)*(v-40+vshift) * valence * (1-memb_fraction) /25 (mV)) rmd2b = Rmd2b * mg * (1e3) * exp((v-40+vshift) * valence * memb_fraction /25 (mV)) rmd2u = Rmd2u * exp((-1)*(v-40+vshift) * valence * (1-memb_fraction) /25 (mV)) ~ U <-> Cl (rb*qfac,Ru*qfac) ~ Cl <-> Open (Ro*qfac,Rc*qfac) ~ Cl <-> D1 (Rd1*qfac,Rr1*qfac) ~ D1 <-> D2 (Rd2*qfac,Rr2*qfac) ~ Open <-> OMg (rmb*qfac,rmu*qfac) ~ UMg <-> ClMg (rbMg*qfac,RuMg*qfac) ~ ClMg <-> OMg (RoMg*qfac,RcMg*qfac) ~ ClMg <-> D1Mg (Rd1Mg*qfac,Rr1Mg*qfac) ~ D1Mg <-> D2Mg (Rd2Mg*qfac,Rr2Mg*qfac) ~ U <-> UMg (rmc1b*qfac,rmc1u*qfac) ~ Cl <-> ClMg (rmc2b*qfac,rmc2u*qfac) ~ D1 <-> D1Mg (rmd1b*qfac,rmd1u*qfac) ~ D2 <-> D2Mg (rmd2b*qfac,rmd2u*qfac) CONSERVE U+Cl+D1+D2+Open+UMg+ClMg+D1Mg+D2Mg+OMg = 1 }