/* Created by Language version: 7.7.0 */
/* NOT VECTORIZED */
#define NRN_VECTORIZED 0
#include <stdio.h>
#include <stdlib.h>
#include <math.h>
#include "scoplib_ansi.h"
#undef PI
#define nil 0
#include "md1redef.h"
#include "section.h"
#include "nrniv_mf.h"
#include "md2redef.h"
#if METHOD3
extern int _method3;
#endif
#if !NRNGPU
#undef exp
#define exp hoc_Exp
extern double hoc_Exp(double);
#endif
#define nrn_init _nrn_init__GABAB
#define _nrn_initial _nrn_initial__GABAB
#define nrn_cur _nrn_cur__GABAB
#define _nrn_current _nrn_current__GABAB
#define nrn_jacob _nrn_jacob__GABAB
#define nrn_state _nrn_state__GABAB
#define _net_receive _net_receive__GABAB
#define bindkin bindkin__GABAB
#define _threadargscomma_ /**/
#define _threadargsprotocomma_ /**/
#define _threadargs_ /**/
#define _threadargsproto_ /**/
/*SUPPRESS 761*/
/*SUPPRESS 762*/
/*SUPPRESS 763*/
/*SUPPRESS 765*/
extern double *getarg();
static double *_p; static Datum *_ppvar;
#define t nrn_threads->_t
#define dt nrn_threads->_dt
#define i _p[0]
#define g _p[1]
#define R _p[2]
#define Ron _p[3]
#define Roff _p[4]
#define G _p[5]
#define Gn _p[6]
#define edc _p[7]
#define synon _p[8]
#define Rinf _p[9]
#define Rtau _p[10]
#define Beta _p[11]
#define DRon _p[12]
#define DRoff _p[13]
#define DG _p[14]
#define _g _p[15]
#define _tsav _p[16]
#define _nd_area *_ppvar[0]._pval
#if MAC
#if !defined(v)
#define v _mlhv
#endif
#if !defined(h)
#define h _mlhh
#endif
#endif
#if defined(__cplusplus)
extern "C" {
#endif
static int hoc_nrnpointerindex = -1;
/* external NEURON variables */
/* declaration of user functions */
static int _mechtype;
extern void _nrn_cacheloop_reg(int, int);
extern void hoc_register_prop_size(int, int, int);
extern void hoc_register_limits(int, HocParmLimits*);
extern void hoc_register_units(int, HocParmUnits*);
extern void nrn_promote(Prop*, int, int);
extern Memb_func* memb_func;
#define NMODL_TEXT 1
#if NMODL_TEXT
static const char* nmodl_file_text;
static const char* nmodl_filename;
extern void hoc_reg_nmodl_text(int, const char*);
extern void hoc_reg_nmodl_filename(int, const char*);
#endif
extern Prop* nrn_point_prop_;
static int _pointtype;
static void* _hoc_create_pnt(_ho) Object* _ho; { void* create_point_process();
return create_point_process(_pointtype, _ho);
}
static void _hoc_destroy_pnt();
static double _hoc_loc_pnt(_vptr) void* _vptr; {double loc_point_process();
return loc_point_process(_pointtype, _vptr);
}
static double _hoc_has_loc(_vptr) void* _vptr; {double has_loc_point();
return has_loc_point(_vptr);
}
static double _hoc_get_loc_pnt(_vptr)void* _vptr; {
double get_loc_point_process(); return (get_loc_point_process(_vptr));
}
extern void _nrn_setdata_reg(int, void(*)(Prop*));
static void _setdata(Prop* _prop) {
_p = _prop->param; _ppvar = _prop->dparam;
}
static void _hoc_setdata(void* _vptr) { Prop* _prop;
_prop = ((Point_process*)_vptr)->_prop;
_setdata(_prop);
}
/* connect user functions to hoc names */
static VoidFunc hoc_intfunc[] = {
0,0
};
static Member_func _member_func[] = {
"loc", _hoc_loc_pnt,
"has_loc", _hoc_has_loc,
"get_loc", _hoc_get_loc_pnt,
0, 0
};
/* declare global and static user variables */
#define Cdur Cdur_GABAB
double Cdur = 0.3;
#define Cmax Cmax_GABAB
double Cmax = 0.5;
#define Erev Erev_GABAB
double Erev = -95;
#define KD KD_GABAB
double KD = 100;
#define K4 K4_GABAB
double K4 = 0.033;
#define K3 K3_GABAB
double K3 = 0.098;
#define K2 K2_GABAB
double K2 = 0.0013;
#define K1 K1_GABAB
double K1 = 0.52;
#define cutoff cutoff_GABAB
double cutoff = 1e+12;
#define n n_GABAB
double n = 4;
#define warn warn_GABAB
double warn = 0;
/* some parameters have upper and lower limits */
static HocParmLimits _hoc_parm_limits[] = {
0,0,0
};
static HocParmUnits _hoc_parm_units[] = {
"Cmax_GABAB", "mM",
"Cdur_GABAB", "ms",
"K1_GABAB", "/ms",
"K2_GABAB", "/ms",
"K3_GABAB", "/ms",
"K4_GABAB", "/ms",
"Erev_GABAB", "mV",
"i", "nA",
"g", "umho",
0,0
};
static double G0 = 0;
static double Roff0 = 0;
static double Ron0 = 0;
static double delta_t = 1;
static double v = 0;
/* connect global user variables to hoc */
static DoubScal hoc_scdoub[] = {
"Cmax_GABAB", &Cmax_GABAB,
"Cdur_GABAB", &Cdur_GABAB,
"K1_GABAB", &K1_GABAB,
"K2_GABAB", &K2_GABAB,
"K3_GABAB", &K3_GABAB,
"K4_GABAB", &K4_GABAB,
"KD_GABAB", &KD_GABAB,
"n_GABAB", &n_GABAB,
"Erev_GABAB", &Erev_GABAB,
"warn_GABAB", &warn_GABAB,
"cutoff_GABAB", &cutoff_GABAB,
0,0
};
static DoubVec hoc_vdoub[] = {
0,0,0
};
static double _sav_indep;
static void nrn_alloc(Prop*);
static void nrn_init(_NrnThread*, _Memb_list*, int);
static void nrn_state(_NrnThread*, _Memb_list*, int);
static void nrn_cur(_NrnThread*, _Memb_list*, int);
static void nrn_jacob(_NrnThread*, _Memb_list*, int);
static void _hoc_destroy_pnt(_vptr) void* _vptr; {
destroy_point_process(_vptr);
}
static int _ode_count(int);
static void _ode_map(int, double**, double**, double*, Datum*, double*, int);
static void _ode_spec(_NrnThread*, _Memb_list*, int);
static void _ode_matsol(_NrnThread*, _Memb_list*, int);
#define _cvode_ieq _ppvar[3]._i
static void _ode_matsol_instance1(_threadargsproto_);
/* connect range variables in _p that hoc is supposed to know about */
static const char *_mechanism[] = {
"7.7.0",
"GABAB",
0,
"i",
"g",
"R",
0,
"Ron",
"Roff",
"G",
0,
0};
extern Prop* need_memb(Symbol*);
static void nrn_alloc(Prop* _prop) {
Prop *prop_ion;
double *_p; Datum *_ppvar;
if (nrn_point_prop_) {
_prop->_alloc_seq = nrn_point_prop_->_alloc_seq;
_p = nrn_point_prop_->param;
_ppvar = nrn_point_prop_->dparam;
}else{
_p = nrn_prop_data_alloc(_mechtype, 17, _prop);
/*initialize range parameters*/
}
_prop->param = _p;
_prop->param_size = 17;
if (!nrn_point_prop_) {
_ppvar = nrn_prop_datum_alloc(_mechtype, 4, _prop);
}
_prop->dparam = _ppvar;
/*connect ionic variables to this model*/
}
static void _initlists();
/* some states have an absolute tolerance */
static Symbol** _atollist;
static HocStateTolerance _hoc_state_tol[] = {
0,0
};
#define _tqitem &(_ppvar[2]._pvoid)
static void _net_receive(Point_process*, double*, double);
extern Symbol* hoc_lookup(const char*);
extern void _nrn_thread_reg(int, int, void(*)(Datum*));
extern void _nrn_thread_table_reg(int, void(*)(double*, Datum*, Datum*, _NrnThread*, int));
extern void hoc_register_tolerance(int, HocStateTolerance*, Symbol***);
extern void _cvode_abstol( Symbol**, double*, int);
void _gabab_reg() {
int _vectorized = 0;
_initlists();
_pointtype = point_register_mech(_mechanism,
nrn_alloc,nrn_cur, nrn_jacob, nrn_state, nrn_init,
hoc_nrnpointerindex, 0,
_hoc_create_pnt, _hoc_destroy_pnt, _member_func);
_mechtype = nrn_get_mechtype(_mechanism[1]);
_nrn_setdata_reg(_mechtype, _setdata);
#if NMODL_TEXT
hoc_reg_nmodl_text(_mechtype, nmodl_file_text);
hoc_reg_nmodl_filename(_mechtype, nmodl_filename);
#endif
hoc_register_prop_size(_mechtype, 17, 4);
hoc_register_dparam_semantics(_mechtype, 0, "area");
hoc_register_dparam_semantics(_mechtype, 1, "pntproc");
hoc_register_dparam_semantics(_mechtype, 2, "netsend");
hoc_register_dparam_semantics(_mechtype, 3, "cvodeieq");
hoc_register_cvode(_mechtype, _ode_count, _ode_map, _ode_spec, _ode_matsol);
hoc_register_tolerance(_mechtype, _hoc_state_tol, &_atollist);
pnt_receive[_mechtype] = _net_receive;
pnt_receive_size[_mechtype] = 3;
hoc_register_var(hoc_scdoub, hoc_vdoub, hoc_intfunc);
ivoc_help("help ?1 GABAB /Users/salvadord/Documents/ISB/Models/M1_NetPyNE_CellReports_2023/sim/mod/gabab.mod\n");
hoc_register_limits(_mechtype, _hoc_parm_limits);
hoc_register_units(_mechtype, _hoc_parm_units);
}
static int _reset;
static char *modelname = "";
static int error;
static int _ninits = 0;
static int _match_recurse=1;
static void _modl_cleanup(){ _match_recurse=1;}
static int _deriv1_advance = 0;
static int _ode_spec1(_threadargsproto_);
/*static int _ode_matsol1(_threadargsproto_);*/
static int _slist2[3]; static double _dlist2[3];
static double _savstate1[3], *_temp1 = _savstate1;
static int _slist1[3], _dlist1[3];
static int bindkin(_threadargsproto_);
/*CVODE*/
static int _ode_spec1 () {_reset=0;
{
DRon = synon * K1 * Cmax - ( K1 * Cmax + K2 ) * Ron ;
DRoff = - K2 * Roff ;
R = Ron + Roff ;
DG = K3 * R - K4 * G ;
}
return _reset;
}
static int _ode_matsol1 () {
DRon = DRon / (1. - dt*( ( - ( ( K1 * Cmax + K2 ) )*( 1.0 ) ) )) ;
DRoff = DRoff / (1. - dt*( ( - K2 )*( 1.0 ) )) ;
R = Ron + Roff ;
DG = DG / (1. - dt*( ( - ( K4 )*( 1.0 ) ) )) ;
return 0;
}
/*END CVODE*/
static int bindkin () {_reset=0;
{ static int _recurse = 0;
int _counte = -1;
if (!_recurse) {
_recurse = 1;
{int _id; for(_id=0; _id < 3; _id++) { _savstate1[_id] = _p[_slist1[_id]];}}
error = newton(3,_slist2, _p, bindkin, _dlist2);
_recurse = 0; if(error) {abort_run(error);}}
{
DRon = synon * K1 * Cmax - ( K1 * Cmax + K2 ) * Ron ;
DRoff = - K2 * Roff ;
R = Ron + Roff ;
DG = K3 * R - K4 * G ;
{int _id; for(_id=0; _id < 3; _id++) {
if (_deriv1_advance) {
_dlist2[++_counte] = _p[_dlist1[_id]] - (_p[_slist1[_id]] - _savstate1[_id])/dt;
}else{
_dlist2[++_counte] = _p[_slist1[_id]] - _savstate1[_id];}}}
} }
return _reset;}
static void _net_receive (_pnt, _args, _lflag) Point_process* _pnt; double* _args; double _lflag;
{ _p = _pnt->_prop->param; _ppvar = _pnt->_prop->dparam;
if (_tsav > t){ extern char* hoc_object_name(); hoc_execerror(hoc_object_name(_pnt->ob), ":Event arrived out of order. Must call ParallelContext.set_maxstep AFTER assigning minimum NetCon.delay");}
_tsav = t; if (_lflag == 1. ) {*(_tqitem) = 0;}
{
if ( _lflag == 1.0 ) {
_args[1] = _args[0] * ( Rinf + ( _args[1] - Rinf ) * exp ( - ( t - _args[2] ) / Rtau ) ) ;
_args[2] = t ;
synon = synon - _args[0] ;
if (nrn_netrec_state_adjust && !cvode_active_){
/* discon state adjustment for general derivimplicit and KINETIC case */
int __i, __neq = 3;
double __state = Ron;
double __primary_delta = (Ron - _args[1] ) - __state;
double __dtsav = dt;
for (__i = 0; __i < __neq; ++__i) {
_p[_dlist1[__i]] = 0.0;
}
_p[_dlist1[0]] = __primary_delta;
dt *= 0.5;
v = NODEV(_pnt->node);
#if NRN_VECTORIZED
_thread = _nt->_ml_list[_mechtype]->_thread;
#endif
_ode_matsol_instance1(_threadargs_);
dt = __dtsav;
for (__i = 0; __i < __neq; ++__i) {
_p[_slist1[__i]] += _p[_dlist1[__i]];
}
} else {
Ron = Ron - _args[1] ;
}
if (nrn_netrec_state_adjust && !cvode_active_){
/* discon state adjustment for general derivimplicit and KINETIC case */
int __i, __neq = 3;
double __state = Roff;
double __primary_delta = (Roff + _args[1] ) - __state;
double __dtsav = dt;
for (__i = 0; __i < __neq; ++__i) {
_p[_dlist1[__i]] = 0.0;
}
_p[_dlist1[1]] = __primary_delta;
dt *= 0.5;
v = NODEV(_pnt->node);
#if NRN_VECTORIZED
_thread = _nt->_ml_list[_mechtype]->_thread;
#endif
_ode_matsol_instance1(_threadargs_);
dt = __dtsav;
for (__i = 0; __i < __neq; ++__i) {
_p[_slist1[__i]] += _p[_dlist1[__i]];
}
} else {
Roff = Roff + _args[1] ;
}
}
else {
_args[1] = _args[0] * _args[1] * exp ( - Beta * ( t - _args[2] ) ) ;
_args[2] = t ;
synon = synon + _args[0] ;
if (nrn_netrec_state_adjust && !cvode_active_){
/* discon state adjustment for general derivimplicit and KINETIC case */
int __i, __neq = 3;
double __state = Ron;
double __primary_delta = (Ron + _args[1] ) - __state;
double __dtsav = dt;
for (__i = 0; __i < __neq; ++__i) {
_p[_dlist1[__i]] = 0.0;
}
_p[_dlist1[0]] = __primary_delta;
dt *= 0.5;
v = NODEV(_pnt->node);
#if NRN_VECTORIZED
_thread = _nt->_ml_list[_mechtype]->_thread;
#endif
_ode_matsol_instance1(_threadargs_);
dt = __dtsav;
for (__i = 0; __i < __neq; ++__i) {
_p[_slist1[__i]] += _p[_dlist1[__i]];
}
} else {
Ron = Ron + _args[1] ;
}
if (nrn_netrec_state_adjust && !cvode_active_){
/* discon state adjustment for general derivimplicit and KINETIC case */
int __i, __neq = 3;
double __state = Roff;
double __primary_delta = (Roff - _args[1] ) - __state;
double __dtsav = dt;
for (__i = 0; __i < __neq; ++__i) {
_p[_dlist1[__i]] = 0.0;
}
_p[_dlist1[1]] = __primary_delta;
dt *= 0.5;
v = NODEV(_pnt->node);
#if NRN_VECTORIZED
_thread = _nt->_ml_list[_mechtype]->_thread;
#endif
_ode_matsol_instance1(_threadargs_);
dt = __dtsav;
for (__i = 0; __i < __neq; ++__i) {
_p[_slist1[__i]] += _p[_dlist1[__i]];
}
} else {
Roff = Roff - _args[1] ;
}
net_send ( _tqitem, _args, _pnt, t + Cdur , 1.0 ) ;
}
} }
static int _ode_count(int _type){ return 3;}
static void _ode_spec(_NrnThread* _nt, _Memb_list* _ml, int _type) {
Datum* _thread;
Node* _nd; double _v; int _iml, _cntml;
_cntml = _ml->_nodecount;
_thread = _ml->_thread;
for (_iml = 0; _iml < _cntml; ++_iml) {
_p = _ml->_data[_iml]; _ppvar = _ml->_pdata[_iml];
_nd = _ml->_nodelist[_iml];
v = NODEV(_nd);
_ode_spec1 ();
}}
static void _ode_map(int _ieq, double** _pv, double** _pvdot, double* _pp, Datum* _ppd, double* _atol, int _type) {
int _i; _p = _pp; _ppvar = _ppd;
_cvode_ieq = _ieq;
for (_i=0; _i < 3; ++_i) {
_pv[_i] = _pp + _slist1[_i]; _pvdot[_i] = _pp + _dlist1[_i];
_cvode_abstol(_atollist, _atol, _i);
}
}
static void _ode_matsol_instance1(_threadargsproto_) {
_ode_matsol1 ();
}
static void _ode_matsol(_NrnThread* _nt, _Memb_list* _ml, int _type) {
Datum* _thread;
Node* _nd; double _v; int _iml, _cntml;
_cntml = _ml->_nodecount;
_thread = _ml->_thread;
for (_iml = 0; _iml < _cntml; ++_iml) {
_p = _ml->_data[_iml]; _ppvar = _ml->_pdata[_iml];
_nd = _ml->_nodelist[_iml];
v = NODEV(_nd);
_ode_matsol_instance1(_threadargs_);
}}
static void initmodel() {
int _i; double _save;_ninits++;
_save = t;
t = 0.0;
{
G = G0;
Roff = Roff0;
Ron = Ron0;
{
R = 0.0 ;
G = 0.0 ;
Ron = 0.0 ;
Roff = 0.0 ;
synon = 0.0 ;
Rinf = K1 * Cmax / ( K1 * Cmax + K2 ) ;
Rtau = 1.0 / ( K1 * Cmax + K2 ) ;
Beta = K2 ;
}
_sav_indep = t; t = _save;
}
}
static void nrn_init(_NrnThread* _nt, _Memb_list* _ml, int _type){
Node *_nd; double _v; int* _ni; int _iml, _cntml;
#if CACHEVEC
_ni = _ml->_nodeindices;
#endif
_cntml = _ml->_nodecount;
for (_iml = 0; _iml < _cntml; ++_iml) {
_p = _ml->_data[_iml]; _ppvar = _ml->_pdata[_iml];
_tsav = -1e20;
#if CACHEVEC
if (use_cachevec) {
_v = VEC_V(_ni[_iml]);
}else
#endif
{
_nd = _ml->_nodelist[_iml];
_v = NODEV(_nd);
}
v = _v;
initmodel();
}}
static double _nrn_current(double _v){double _current=0.;v=_v;{ {
if ( G < cutoff ) {
Gn = G * G * G * G ;
g = Gn / ( Gn + KD ) ;
}
else {
if ( ! warn ) {
printf ( "gabab.mod WARN: G = %g too large\n" , G ) ;
warn = 1.0 ;
}
g = 1.0 ;
}
i = g * ( v - Erev ) ;
}
_current += i;
} return _current;
}
static void nrn_cur(_NrnThread* _nt, _Memb_list* _ml, int _type){
Node *_nd; int* _ni; double _rhs, _v; int _iml, _cntml;
#if CACHEVEC
_ni = _ml->_nodeindices;
#endif
_cntml = _ml->_nodecount;
for (_iml = 0; _iml < _cntml; ++_iml) {
_p = _ml->_data[_iml]; _ppvar = _ml->_pdata[_iml];
#if CACHEVEC
if (use_cachevec) {
_v = VEC_V(_ni[_iml]);
}else
#endif
{
_nd = _ml->_nodelist[_iml];
_v = NODEV(_nd);
}
_g = _nrn_current(_v + .001);
{ _rhs = _nrn_current(_v);
}
_g = (_g - _rhs)/.001;
_g *= 1.e2/(_nd_area);
_rhs *= 1.e2/(_nd_area);
#if CACHEVEC
if (use_cachevec) {
VEC_RHS(_ni[_iml]) -= _rhs;
}else
#endif
{
NODERHS(_nd) -= _rhs;
}
}}
static void nrn_jacob(_NrnThread* _nt, _Memb_list* _ml, int _type){
Node *_nd; int* _ni; int _iml, _cntml;
#if CACHEVEC
_ni = _ml->_nodeindices;
#endif
_cntml = _ml->_nodecount;
for (_iml = 0; _iml < _cntml; ++_iml) {
_p = _ml->_data[_iml];
#if CACHEVEC
if (use_cachevec) {
VEC_D(_ni[_iml]) += _g;
}else
#endif
{
_nd = _ml->_nodelist[_iml];
NODED(_nd) += _g;
}
}}
static void nrn_state(_NrnThread* _nt, _Memb_list* _ml, int _type){
Node *_nd; double _v = 0.0; int* _ni; int _iml, _cntml;
double _dtsav = dt;
if (secondorder) { dt *= 0.5; }
#if CACHEVEC
_ni = _ml->_nodeindices;
#endif
_cntml = _ml->_nodecount;
for (_iml = 0; _iml < _cntml; ++_iml) {
_p = _ml->_data[_iml]; _ppvar = _ml->_pdata[_iml];
_nd = _ml->_nodelist[_iml];
#if CACHEVEC
if (use_cachevec) {
_v = VEC_V(_ni[_iml]);
}else
#endif
{
_nd = _ml->_nodelist[_iml];
_v = NODEV(_nd);
}
v=_v;
{
{ error = _deriv1_advance = 1;
derivimplicit(_ninits, 3, _slist1, _dlist1, _p, &t, dt, bindkin, &_temp1);
_deriv1_advance = 0;
if(error){fprintf(stderr,"at line 168 in file gabab.mod:\n SOLVE bindkin METHOD derivimplicit\n"); nrn_complain(_p); abort_run(error);}
if (secondorder) {
int _i;
for (_i = 0; _i < 3; ++_i) {
_p[_slist1[_i]] += dt*_p[_dlist1[_i]];
}}
}}}
dt = _dtsav;
}
static void terminal(){}
static void _initlists() {
int _i; static int _first = 1;
if (!_first) return;
_slist1[0] = &(Ron) - _p; _dlist1[0] = &(DRon) - _p;
_slist1[1] = &(Roff) - _p; _dlist1[1] = &(DRoff) - _p;
_slist1[2] = &(G) - _p; _dlist1[2] = &(DG) - _p;
_slist2[0] = &(G) - _p;
_slist2[1] = &(Roff) - _p;
_slist2[2] = &(Ron) - _p;
_first = 0;
}
#if NMODL_TEXT
static const char* nmodl_filename = "/Users/salvadord/Documents/ISB/Models/M1_NetPyNE_CellReports_2023/sim/mod/gabab.mod";
static const char* nmodl_file_text =
": $Id: gabab.mod,v 1.9 2004/06/17 16:04:05 billl Exp $\n"
"\n"
"COMMENT\n"
"-----------------------------------------------------------------------------\n"
"\n"
" Kinetic model of GABA-B receptors\n"
" =================================\n"
"\n"
" MODEL OF SECOND-ORDER G-PROTEIN TRANSDUCTION AND FAST K+ OPENING\n"
" WITH COOPERATIVITY OF G-PROTEIN BINDING TO K+ CHANNEL\n"
"\n"
" PULSE OF TRANSMITTER\n"
"\n"
" SIMPLE KINETICS WITH NO DESENSITIZATION\n"
"\n"
" Features:\n"
"\n"
" - peak at 100 ms; time course fit to Tom Otis' PSC\n"
" - SUMMATION (psc is much stronger with bursts)\n"
"\n"
"\n"
" Approximations:\n"
"\n"
" - single binding site on receptor \n"
" - model of alpha G-protein activation (direct) of K+ channel\n"
" - G-protein dynamics is second-order; simplified as follows:\n"
" - saturating receptor\n"
" - no desensitization\n"
" - Michaelis-Menten of receptor for G-protein production\n"
" - \"resting\" G-protein is in excess\n"
" - Quasi-stat of intermediate enzymatic forms\n"
" - binding on K+ channel is fast\n"
"\n"
"\n"
" Kinetic Equations:\n"
"\n"
" dR/dt = K1 * T * (1-R-D) - K2 * R\n"
"\n"
" dG/dt = K3 * R - K4 * G\n"
"\n"
" R : activated receptor\n"
" T : transmitter\n"
" G : activated G-protein\n"
" K1,K2,K3,K4 = kinetic rate cst\n"
"\n"
" n activated G-protein bind to a K+ channel:\n"
"\n"
" n G + C <-> O (Alpha,Beta)\n"
"\n"
" If the binding is fast, the fraction of open channels is given by:\n"
"\n"
" O = G^n / ( G^n + KD )\n"
"\n"
" where KD = Beta / Alpha is the dissociation constant\n"
"\n"
"-----------------------------------------------------------------------------\n"
"\n"
" Parameters estimated from patch clamp recordings of GABAB PSP's in\n"
" rat hippocampal slices (Otis et al, J. Physiol. 463: 391-407, 1993).\n"
"\n"
"-----------------------------------------------------------------------------\n"
"\n"
" PULSE MECHANISM\n"
"\n"
" Kinetic synapse with release mechanism as a pulse. \n"
"\n"
" Warning: for this mechanism to be equivalent to the model with diffusion \n"
" of transmitter, small pulses must be used...\n"
"\n"
" For a detailed model of GABAB:\n"
"\n"
" Destexhe, A. and Sejnowski, T.J. G-protein activation kinetics and\n"
" spill-over of GABA may account for differences between inhibitory responses\n"
" in the hippocampus and thalamus. Proc. Natl. Acad. Sci. USA 92:\n"
" 9515-9519, 1995.\n"
"\n"
" For a review of models of synaptic currents:\n"
"\n"
" Destexhe, A., Mainen, Z.F. and Sejnowski, T.J. Kinetic models of \n"
" synaptic transmission. In: Methods in Neuronal Modeling (2nd edition; \n"
" edited by Koch, C. and Segev, I.), MIT press, Cambridge, 1996.\n"
"\n"
" This simplified model was introduced in:\n"
"\n"
" Destexhe, A., Bal, T., McCormick, D.A. and Sejnowski, T.J.\n"
" Ionic mechanisms underlying synchronized oscillations and propagating\n"
" waves in a model of ferret thalamic slices. Journal of Neurophysiology\n"
" 76: 2049-2070, 1996. \n"
"\n"
" See also http://www.cnl.salk.edu/~alain\n"
"\n"
"\n"
"\n"
" Alain Destexhe, Salk Institute and Laval University, 1995\n"
"\n"
"-----------------------------------------------------------------------------\n"
"ENDCOMMENT\n"
"\n"
"\n"
"\n"
"INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}\n"
"\n"
"NEURON {\n"
" POINT_PROCESS GABAB\n"
" RANGE R, G, g\n"
" NONSPECIFIC_CURRENT i\n"
" GLOBAL Cmax, Cdur\n"
" GLOBAL K1, K2, K3, K4, KD, Erev, warn, cutoff\n"
"}\n"
"UNITS {\n"
" (nA) = (nanoamp)\n"
" (mV) = (millivolt)\n"
" (umho) = (micromho)\n"
" (mM) = (milli/liter)\n"
"}\n"
"\n"
"PARAMETER {\n"
"\n"
" Cmax = 0.5 (mM) : max transmitter concentration\n"
" Cdur = 0.3 (ms) : transmitter duration (rising phase)\n"
":\n"
": From Kfit with long pulse (5ms 0.5mM)\n"
":\n"
" K1 = 0.52 (/ms mM) : forward binding rate to receptor\n"
" K2 = 0.0013 (/ms) : backward (unbinding) rate of receptor\n"
" K3 = 0.098 (/ms) : rate of G-protein production\n"
" K4 = 0.033 (/ms) : rate of G-protein decay\n"
" KD = 100 : dissociation constant of K+ channel\n"
" n = 4 : nb of binding sites of G-protein on K+\n"
" Erev = -95 (mV) : reversal potential (E_K)\n"
" warn = 0 : too large G warning has/has not been issued\n"
" cutoff = 1e12\n"
"}\n"
"\n"
"\n"
"ASSIGNED {\n"
" v (mV) : postsynaptic voltage\n"
" i (nA) : current = g*(v - Erev)\n"
" g (umho) : conductance\n"
" Gn\n"
" R : fraction of activated receptor\n"
" edc\n"
" synon\n"
" Rinf\n"
" Rtau (ms)\n"
" Beta (/ms)\n"
"}\n"
"\n"
"STATE {\n"
" Ron Roff\n"
" G : fraction of activated G-protein\n"
"}\n"
"\n"
"\n"
"INITIAL {\n"
" R = 0\n"
" G = 0\n"
" Ron = 0\n"
" Roff = 0\n"
" synon = 0\n"
" Rinf = K1*Cmax/(K1*Cmax + K2)\n"
" Rtau = 1/(K1*Cmax + K2)\n"
" Beta = K2\n"
"\n"
"}\n"
"\n"
"BREAKPOINT {\n"
" SOLVE bindkin METHOD derivimplicit\n"
" if (G < cutoff) {\n"
" Gn = G*G*G*G : ^n = 4\n"
" g = Gn / (Gn+KD)\n"
" } else {\n"
" if(!warn){\n"
" printf(\"gabab.mod WARN: G = %g too large\\n\", G) \n"
" warn = 1\n"
" }\n"
" g = 1\n"
" }\n"
" i = g*(v - Erev)\n"
"}\n"
"\n"
"\n"
"DERIVATIVE bindkin {\n"
" Ron' = synon*K1*Cmax - (K1*Cmax + K2)*Ron\n"
" Roff' = -K2*Roff\n"
" R = Ron + Roff\n"
" G' = K3 * R - K4 * G\n"
"}\n"
"\n"
": following supports both saturation from single input and\n"
": summation from multiple inputs\n"
": Note: automatic initialization of all reference args to 0 except first\n"
"\n"
"NET_RECEIVE(weight, r0, t0 (ms)) {\n"
" if (flag == 1) { : at end of Cdur pulse so turn off\n"
" r0 = weight*(Rinf + (r0 - Rinf)*exp(-(t - t0)/Rtau))\n"
" t0 = t\n"
" synon = synon - weight\n"
" state_discontinuity(Ron, Ron - r0)\n"
" state_discontinuity(Roff, Roff + r0)\n"
" }else{ : at beginning of Cdur pulse so turn on\n"
" r0 = weight*r0*exp(-Beta*(t - t0))\n"
" t0 = t\n"
" synon = synon + weight\n"
" state_discontinuity(Ron, Ron + r0)\n"
" state_discontinuity(Roff, Roff - r0)\n"
" :come again in Cdur\n"
" net_send(Cdur, 1)\n"
" }\n"
"}\n"
;
#endif