You can not select more than 25 topics
Topics must start with a letter or number, can include dashes ('-') and can be up to 35 characters long.
224 lines
6.8 KiB
224 lines
6.8 KiB
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 |
|
}
|
|
|