TITLE Model of AMPA receptors COMMENT ----------------------------------------------------------------------------- Kinetic model of AMPA receptors =============================== 6-state gating model: (scheme 1 from Raman and Trussell, Neuron 9:173-186, 1992) 2 open states provide dual exponential response. O1 | C -- C1 -- C2 -- O2 | D ----------------------------------------------------------------------------- This mod file does not include mechanisms for the release and time course of transmitter; it is to be used in conjunction with a separate mechanism to describe the release of transmitter and that provides the concentration of transmitter in the synaptic cleft (to be connected to pointer C here). Default parameters are set for a miniature EPSC. ----------------------------------------------------------------------------- Code based on Destexhe's ampa5.mod B. Graham, Dept. of Computing Science & Maths, University of Stirling (Contact: b.graham@cs.stir.ac.uk) (previously IANC, Division of Informatics, University of Edinburgh) CNS 2000 Version (19/11/02) ----------------------------------------------------------------------------- Further modified: Paul Manis (Otolaryngology/HNS and Cell and Molecular Physiology, UNC Chapel Hill. contact: pmanis@med.unc.edu) 3/15/2005 Modifications: 1. Added Q10/qfac to allow temperature scaling. All rates in the state model are changed by the same factor. A Q10 of 1.5 gives a decay tau (single exponential fit using Praxis algorithm in NEURON; using ampa_kinetics.hoc) of about 850 usec at 22 deg C and 570 usec at 33 deg C. These are consistent with the Raman and Trussell 1992 measurements in avians. The 850 usec is a bit fast for an EPSC, and could probably be tuned by adjustment of some of the parameters below. 2. Brought several variables out to global (rather than range) so that we can change them - Q10 and gmax in particular. note that gmax is in pS. Only local conductance etc. is in specified as RANGE. 3. Max open probability is less than unity, so a gmax of 2500 yields 100 pA at -60 mV. Therefore scaling by mini size must take this into account. 3/28/2005 Paul B. Manis Added rectification to AMPA R. Rectification is controlled by polyamine-style block of receptor. See Donevan and Rogawski, 1995; Washburn et al., 1997. The equations used here are from Washburn et al. The values given in the equation at the break point were determined from EPSCs in 5 21-d old DBA mice. Blocker = 45 (uM), Kd = 31.32, zd = 1.029. Note that this should also reduce the maximal conductance. Mode: if 1, use rectifying; if 0, use non-rectifying. Default is 1 This point process uses XMTR as the transmitter concentration to operate on the receptor kinetics. XMTR should be provided by another process that controls release (e.g., COH calyx of Held, etc). An advantage of this is that whatever release process is present, glutamate accumulates in the cleft, and can drive desensitization etc. ----------------------------------------------------------------------------- ENDCOMMENT INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)} NEURON { THREADSAFE POINT_PROCESS AMPATRUSSELL POINTER XMTR RANGE C0, C1, C2, D, O1, O2 RANGE Rb, Ru1, Ru2, Rd, Rr, Ro1, Rc1, Ro2, Rc2, Open, MaxOpen GLOBAL vmin, vmax GLOBAL Q10, Mode GLOBAL zd, Kd0 RANGE g, rb, gmax, PA, Erev NONSPECIFIC_CURRENT i } UNITS { (nA) = (nanoamp) (mV) = (millivolt) (pS) = (picosiemens) (umho) = (micromho) (mM) = (milli/liter) (uM) = (micro/liter) } PARAMETER { Erev = 7 (mV) : reversal potential gmax = 10 (pS) : maximal conductance vmin = -120 (mV) vmax = 100 (mV) Q10 = 1.5 : temperature sensitivity Mode = 0 : flag to control rectification calculation : polyamine block parameters (Wang & Manis unpublished data) zd = 1.032 PA = 45 Kd0 = 31.e-6 : Rates Rb = 13 (/mM /ms): binding : diffusion limited (DO NOT ADJUST) Ru1 = 0.3 (/ms) : unbinding (1st site) Ru2 = 200 (/ms) : unbinding (2nd site) Rd = 30.0 (/ms) : desensitization (WAS30.0) Rr = 0.02 (/ms) : resensitization Ro1 = 100 (/ms) : opening (fast) Rc1 = 2 (/ms) : closing Ro2 = 2 (/ms) : opening (slow) Rc2 = 0.25 (/ms) : closing Open = 0 (1) : total of all open states : Maximum open probability with Mode=0 (no rectification). : This is determined empirically by holding XMTR at a large : value for 100 timesteps and measuring the maximum value : of Open. MaxOpen = 0.72418772400 (1) aflag = 1 : Flag for control of printout of initial values..... } ASSIGNED { v (mV) : postsynaptic voltage i (nA) : current = g*(v - Erev) g (pS) : conductance g0 (pS) : conductance for voltage-dependent block by polyamines gvdep (pS) : voltage-dependence of conductance XMTR (mM) : pointer to glutamate concentration rb (/ms) : binding qfac : q10 factor for rate scaling celsius (degC) } STATE { : Channel states (all fractions) C0 : unbound C1 : single glu bound C2 : double glu bound D : single glu bound, desensitized O1 : open state 1 O2 : open state 2 } INITIAL { usetable = 0 C0=1 C1=0 C2=0 D=0 O1=0 O2=0 Open = 0 qfac = Q10^((celsius-22)/10) : VERBATIM : fprintf(stdout, "AMPA.MOD gmax: %f Q10 = %f celsius = %f\n", gmax, Q10, celsius); : ENDVERBATIM gvdepcalc(v) } BREAKPOINT { SOLVE kstates METHOD sparse : VERBATIM : fprintf(stderr, "kstates @ t=%7.2f Rb: %f XMTR: %f: gmax: %f, o1: %f o2: %f\n", t, Rb, XMTR, gmax, O1, O2); : ENDVERBATIM gvdepcalc(v) Open = O1 + O2 g = gmax * Open / MaxOpen if ( Mode == 1) { g0 = 1.0 + 0.6*exp((v-50)/40) : eq. 5 of Washburn et al., 1997, slightly modified gvdep = g0*(1/(1+PA/(Kd0*exp(-zd*v/25.3)))) i = (1e-6) * g * gvdep * (v - Erev) } else { i = (1e-6)*g*(v-Erev) } } KINETIC kstates { rb = Rb * XMTR ~ C0 <-> C1 (rb*qfac,Ru1*qfac) ~ C1 <-> C2 (rb*qfac,Ru2*qfac) ~ C2 <-> D (Rd*qfac,Rr*qfac) ~ C2 <-> O1 (Ro1*qfac,Rc1*qfac) ~ C2 <-> O2 (Ro2*qfac,Rc2*qfac) CONSERVE C0+C1+C2+D+O1+O2 = 1 } LOCAL g0 PROCEDURE gvdepcalc(v) { TABLE gvdep DEPEND PA, Kd0, zd FROM -100 TO 100 WITH 200 : VERBATIM : fprintf(stderr, "gvdepcalc starts "); : ENDVERBATIM g0 = 1.0 + 0.6*exp((v-50)/40) : eq. 5 of Washburn et al., 1997, slightly modified gvdep = g0*(1/(1+PA/(Kd0*exp(-zd*v/25.3)))) : VERBATIM : fprintf(stderr, "& ends\n"); : ENDVERBATIM }