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212 lines
7.0 KiB
212 lines
7.0 KiB
TITLE kinetic NMDA receptor model |
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COMMENT |
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----------------------------------------------------------------------------- |
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Kinetic model of NMDA receptors |
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=============================== |
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10-state gating model: |
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Kampa et al. (2004) J Physiol |
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U -- Cl -- O |
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\ | \ \ |
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\ | \ \ |
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UMg -- ClMg - OMg |
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D1 | |
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| \ | |
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D2 \ | |
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\ D1Mg |
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\ | |
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D2Mg |
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----------------------------------------------------------------------------- |
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Based on voltage-clamp recordings of NMDA receptor-mediated currents in |
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nucleated patches of rat neocortical layer 5 pyramidal neurons (Kampa 2004), |
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this model was fit with AxoGraph directly to experimental recordings in |
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order to obtain the optimal values for the parameters. |
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----------------------------------------------------------------------------- |
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This mod file does not include mechanisms for the release and time course |
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of transmitter; it should to be used in conjunction with a separate mechanism |
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to describe the release of transmitter and timecourse of the concentration |
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of transmitter in the synaptic cleft (to be connected to pointer XMTR here). |
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----------------------------------------------------------------------------- |
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See details of NEURON kinetic models in: |
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Destexhe, A., Mainen, Z.F. and Sejnowski, T.J. Kinetic models of |
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synaptic transmission. In: Methods in Neuronal Modeling (2nd edition; |
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edited by Koch, C. and Segev, I.), MIT press, Cambridge, 1996. |
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Written by Bjoern Kampa in 2004 |
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Lightly modified, Paul Manis 2010. |
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Note that data were taken at 23 deg C |
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Q10 was taken from native receptors: |
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Korinek M, Sedlacek M, Cais O, Dittert I, Vyklicky L Jr. Temperature |
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dependence of N-methyl-D-aspartate receptor channels and N-methyl-D-aspartate |
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receptor excitatory postsynaptic currents. Neuroscience. 2010 Feb |
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3;165(3):736-48. Epub 2009 Oct 31. PubMed PMID: 19883737. |
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ENDCOMMENT |
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INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)} |
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NEURON { |
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THREADSAFE |
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POINT_PROCESS NMDA_Kampa |
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POINTER XMTR |
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RANGE U, Cl, D1, D2, Open, MaxOpen, UMg, ClMg, D1Mg, D2Mg, OMg |
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RANGE g, gmax, vshift, Erev, rb, rmb, rmu, rbMg,rmc1b,rmc1u,rmc2b,rmc2u |
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GLOBAL mg, Rb, Ru, Rd1, Rr1, Rd2, Rr2, Ro, Rc, Rmb, Rmu |
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GLOBAL RbMg, RuMg, Rd1Mg, Rr1Mg, Rd2Mg, Rr2Mg, RoMg, RcMg |
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GLOBAL Rmd1b,Rmd1u,Rmd2b,Rmd2u,rmd1b,rmd1u,rmd2b,rmd2u |
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GLOBAL Rmc1b,Rmc1u,Rmc2b,Rmc2u |
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GLOBAL vmin, vmax, valence, memb_fraction |
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NONSPECIFIC_CURRENT i |
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} |
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UNITS { |
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(nA) = (nanoamp) |
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(mV) = (millivolt) |
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(pS) = (picosiemens) |
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(umho) = (micromho) |
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(mM) = (milli/liter) |
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(uM) = (micro/liter) |
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} |
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PARAMETER { |
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Erev = 5 (mV) : reversal potential |
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gmax = 500 (pS) : maximal conductance |
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mg = 1 (mM) : external magnesium concentration |
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vmin = -120 (mV) |
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vmax = 100 (mV) |
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valence = -2 : parameters of voltage-dependent Mg block |
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memb_fraction = 0.8 |
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vshift = 0.0 (mV) |
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Q10 = 2.0 : temperature sensitivity (see above) |
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: Maximum open probability with Mode=0 (no rectification). |
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: This is determined empirically by holding XMTR at a large |
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: value and v=40mV for 100 timesteps and measuring the |
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: maximum value of Open. |
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MaxOpen = 0.01988893957 (1) |
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: Rates |
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Rb = 10e-3 (/uM /ms) : binding |
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Ru = 5.6e-3 (/ms) : unbinding |
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Ro = 10e-3 (/ms) : opening |
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Rc = 273e-3 (/ms) : closing |
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: Rd1 = 2.2e-3 (/ms) : fast desensitisation |
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Rd1 = 0.1 (/ms) : fast desensitisation |
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Rr1 = 1.6e-3 (/ms) : fast resensitisation |
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: Rd2 = 0.43e-3 (/ms) : slow desensitisation |
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Rd2 = 1e-4 (/ms) : slow desensitisation |
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Rr2 = 0.5e-3 (/ms) : slow resensitisation |
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Rmb = 0.05e-3 (/uM /ms) : Mg binding Open |
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Rmu = 12800e-3 (/ms) : Mg unbinding Open |
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Rmc1b = 0.00005e-3 (/uM /ms) : Mg binding Closed |
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Rmc1u = 2.438312e-3 (/ms) : Mg unbinding Closed |
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Rmc2b = 0.00005e-3 (/uM /ms) : Mg binding Closed2 |
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Rmc2u = 5.041915e-3 (/ms) : Mg unbinding Closed2 |
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Rmd1b = 0.00005e-3 (/uM /ms) : Mg binding Desens1 |
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Rmd1u = 2.98874e-3 (/ms) : Mg unbinding Desens1 |
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Rmd2b = 0.00005e-3 (/uM /ms) : Mg binding Desens2 |
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Rmd2u = 2.953408e-3 (/ms) : Mg unbinding Desens2 |
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RbMg = 10e-3 (/uM /ms) : binding with Mg |
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RuMg = 17.1e-3 (/ms) : unbinding with Mg |
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RoMg = 10e-3 (/ms) : opening with Mg |
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RcMg = 548e-3 (/ms) : closing with Mg |
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Rd1Mg = 2.1e-3 (/ms) : fast desensitisation with Mg |
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Rr1Mg = 0.87e-3 (/ms) : fast resensitisation with Mg |
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Rd2Mg = 0.26e-3 (/ms) : slow desensitisation with Mg |
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Rr2Mg = 0.42e-3 (/ms) : slow resensitisation with Mg |
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} |
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ASSIGNED { |
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v (mV) : postsynaptic voltage |
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i (nA) : current = g*(v - Erev) |
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g (pS) : conductance |
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XMTR (mM) : pointer to glutamate concentration |
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rb (/ms) : binding, [glu] dependent |
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rmb (/ms) : blocking V and [Mg] dependent |
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rmu (/ms) : unblocking V and [Mg] dependent |
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rbMg (/ms) : binding, [glu] dependent |
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rmc1b (/ms) : blocking V and [Mg] dependent |
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rmc1u (/ms) : unblocking V and [Mg] dependent |
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rmc2b (/ms) : blocking V and [Mg] dependent |
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rmc2u (/ms) : unblocking V and [Mg] dependent |
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rmd1b (/ms) : blocking V and [Mg] dependent |
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rmd1u (/ms) : unblocking V and [Mg] dependent |
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rmd2b (/ms) : blocking V and [Mg] dependent |
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rmd2u (/ms) : unblocking V and [Mg] dependent |
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qfac : Q10 |
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celsius (degC) |
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} |
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STATE { |
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: Channel states (all fractions) |
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U : unbound |
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Cl : closed |
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D1 : desensitised 1 |
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D2 : desensitised 2 |
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Open : open |
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UMg : unbound with Mg |
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ClMg : closed with Mg |
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D1Mg : desensitised 1 with Mg |
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D2Mg : desensitised 2 with Mg |
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OMg : open with Mg |
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} |
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INITIAL { |
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U = 1 |
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qfac = Q10^((celsius-23)/10 (degC))} |
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BREAKPOINT { |
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SOLVE kstates METHOD sparse |
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g = gmax * Open / MaxOpen |
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i = (1e-6) * g * (v - Erev) |
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} |
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KINETIC kstates { |
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rb = Rb * (1e3) * XMTR |
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rbMg = RbMg * (1e3) * XMTR |
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rmb = Rmb * mg * (1e3) * exp((v-40+vshift) * valence * memb_fraction /25 (mV)) |
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rmu = Rmu * exp((-1)*(v-40+vshift) * valence * (1-memb_fraction) /25 (mV)) |
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rmc1b = Rmc1b * mg * (1e3) * exp((v-40+vshift) * valence * memb_fraction /25 (mV)) |
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rmc1u = Rmc1u * exp((-1)*(v-40+vshift) * valence * (1-memb_fraction) /25 (mV)) |
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rmc2b = Rmc2b * mg * (1e3) * exp((v-40+vshift) * valence * memb_fraction /25 (mV)) |
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rmc2u = Rmc2u * exp((-1)*(v-40+vshift) * valence * (1-memb_fraction) /25 (mV)) |
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rmd1b = Rmd1b * mg * (1e3) * exp((v-40+vshift) * valence * memb_fraction /25 (mV)) |
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rmd1u = Rmd1u * exp((-1)*(v-40+vshift) * valence * (1-memb_fraction) /25 (mV)) |
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rmd2b = Rmd2b * mg * (1e3) * exp((v-40+vshift) * valence * memb_fraction /25 (mV)) |
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rmd2u = Rmd2u * exp((-1)*(v-40+vshift) * valence * (1-memb_fraction) /25 (mV)) |
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~ U <-> Cl (rb*qfac,Ru*qfac) |
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~ Cl <-> Open (Ro*qfac,Rc*qfac) |
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~ Cl <-> D1 (Rd1*qfac,Rr1*qfac) |
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~ D1 <-> D2 (Rd2*qfac,Rr2*qfac) |
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~ Open <-> OMg (rmb*qfac,rmu*qfac) |
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~ UMg <-> ClMg (rbMg*qfac,RuMg*qfac) |
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~ ClMg <-> OMg (RoMg*qfac,RcMg*qfac) |
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~ ClMg <-> D1Mg (Rd1Mg*qfac,Rr1Mg*qfac) |
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~ D1Mg <-> D2Mg (Rd2Mg*qfac,Rr2Mg*qfac) |
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~ U <-> UMg (rmc1b*qfac,rmc1u*qfac) |
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~ Cl <-> ClMg (rmc2b*qfac,rmc2u*qfac) |
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~ D1 <-> D1Mg (rmd1b*qfac,rmd1u*qfac) |
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~ D2 <-> D2Mg (rmd2b*qfac,rmd2u*qfac) |
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CONSERVE U+Cl+D1+D2+Open+UMg+ClMg+D1Mg+D2Mg+OMg = 1 |
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}
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