// DOQCS : http://doqcs.ncbs.res.in/ // Accession Name = Kuroda_GC // Accession Number = 18 // Transcriber = Sudhir Sivakumaran, NCBS // Developer = Shinya Kuroda, Nicolas Schweighofer and Mitsuo Kawato. // Species = Generic mammalian // Tissue = Neuronal // Cell Compartment = Synapse // Notes = This model of sGC is based on the paper by Kuroda S. et al. J Neurosci. (2001) 21(15):5693-702. This models features the activation of sGC by NO, synthesis of cGMP, activity of PKG and PP2A in the synapse. The rates and concentrations have been taken from published literature. //genesis // kkit Version 11 flat dumpfile // Saved on Thu Dec 8 14:49:44 2005 include kkit {argv 1} FASTDT = 1e-05 SIMDT = 0.01 CONTROLDT = 5 PLOTDT = 1 MAXTIME = 1000 TRANSIENT_TIME = 30 VARIABLE_DT_FLAG = 1 DEFAULT_VOL = 1.6667e-21 VERSION = 11.0 setfield /file/modpath value /home2/bhalla/scripts/modules kparms //genesis initdump -version 3 -ignoreorphans 1 simobjdump doqcsinfo filename accessname accesstype transcriber developer \ citation species tissue cellcompartment methodology sources \ model_implementation model_validation x y z simobjdump table input output alloced step_mode stepsize x y z simobjdump xtree path script namemode sizescale simobjdump xcoredraw xmin xmax ymin ymax simobjdump xtext editable simobjdump xgraph xmin xmax ymin ymax overlay simobjdump xplot pixflags script fg ysquish do_slope wy simobjdump group xtree_fg_req xtree_textfg_req plotfield expanded movealone \ link savename file version md5sum mod_save_flag x y z simobjdump geometry size dim shape outside xtree_fg_req xtree_textfg_req x y \ z simobjdump kpool DiffConst CoInit Co n nInit mwt nMin vol slave_enable \ geomname xtree_fg_req xtree_textfg_req x y z simobjdump kreac kf kb notes xtree_fg_req xtree_textfg_req x y z simobjdump kenz CoComplexInit CoComplex nComplexInit nComplex vol k1 k2 k3 \ keepconc usecomplex notes xtree_fg_req xtree_textfg_req link x y z simobjdump stim level1 width1 delay1 level2 width2 delay2 baselevel trig_time \ trig_mode notes xtree_fg_req xtree_textfg_req is_running x y z simobjdump xtab input output alloced step_mode stepsize notes editfunc \ xtree_fg_req xtree_textfg_req baselevel last_x last_y is_running x y z simobjdump kchan perm gmax Vm is_active use_nernst notes xtree_fg_req \ xtree_textfg_req x y z simobjdump transport input output alloced step_mode stepsize dt delay clock \ kf xtree_fg_req xtree_textfg_req x y z simobjdump proto x y z simundump geometry /kinetics/geometry 0 1.6667e-21 3 sphere "" white black 14 \ 5 0 simundump kpool /kinetics/GC 0 0 3 3 3 3 0 0 1 4 /kinetics/geometry 0 black 4 \ 2 0 simundump kpool /kinetics/NO 0 0 0.1 0.1 0.1 0.1 0 0 1 0 /kinetics/geometry \ 62 black 4 4 0 simundump kpool /kinetics/NO_GC 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry 47 \ black 8 3 0 simundump kenz /kinetics/NO_GC/kenz 0 0 0 0 0 1 0.81667 29.4 7.35 0 0 "" red \ 47 "" 8 2 0 simundump kreac /kinetics/NObindGC 0 0.01 0.0025 "" white black 6 3 0 simundump kreac /kinetics/degradeNO 0 0.673 0 "" white black 6 5 0 simundump kpool /kinetics/NOdegrade 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry 27 \ black 10 5 0 simundump kpool /kinetics/GTP 0 0 10 10 10 10 0 0 1 0 /kinetics/geometry 33 \ black 6 0 0 simundump kpool /kinetics/cGMP 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry 52 \ black 10 0 0 simundump kpool /kinetics/PDE 0 0 5 5 5 5 0 0 1 0 /kinetics/geometry 22 black \ 11 3 0 simundump kenz /kinetics/PDE/kenz 0 0 0 0 0 1 9.675 15.48 3.87 0 0 "" red 22 \ "" 11 2 0 simundump kpool /kinetics/PKG 0 0 2.5 2.5 2.5 2.5 0 0 1 0 /kinetics/geometry \ 36 black 14 0 0 simundump kreac /kinetics/cGMPbindPKG 0 10 0.5 "" white black 12 -2 0 simundump kpool /kinetics/cGMP.PKG 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry 56 \ black 12 -4 0 simundump kenz /kinetics/cGMP.PKG/kenz 0 0 0 0 0 1 18 2.88 0.72 0 0 "" red 56 \ "" 10 -4 0 simundump kpool /kinetics/Gsub 0 0 10.7 10.7 10.7 10.7 0 0 1 0 \ /kinetics/geometry 25 black 12 -6 0 simundump kpool /kinetics/Gsub* 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry 48 \ black 7 -4 0 simundump kpool /kinetics/PP2A 0 0 2.7 2.7 2.7 2.7 0 0 1 0 /kinetics/geometry \ 10 black 4 -2 0 simundump kpool /kinetics/PP2A_Gsub* 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry \ 58 black 4 -6 0 simundump kreac /kinetics/PP2AbindGsub* 0 1 0.27 "" white black 4 -4 0 simundump kreac /kinetics/dephosphory 0 1e-04 0 "" white black 8 -6 0 simundump doqcsinfo /kinetics/doqcsinfo 0 db18.g Kuroda_GC pathway \ "Sudhir Sivakumaran, NCBS" \ " Shinya Kuroda, Nicolas Schweighofer and Mitsuo Kawato." "citation here" \ "Generic Mammalian" Neuronal Synapse "Quantitative match to experiments" \ "Kuroda S. et al. J Neurosci. (2001) 21(15):5693-702( Peer-reviewed publication)" \ "Exact GENESIS implementation" "Approximates original data " 14 6 0 simundump kpool /kinetics/5prime_GMP 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry 5 \ black 14 2 0 simundump xgraph /graphs/conc1 0 0 1000 6.73e-07 0.099627 0 simundump xgraph /graphs/conc2 0 0 1000 3e-08 0.0034359 0 simundump xplot /graphs/conc1/NOdegrade.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 27 0 0 1 simundump xplot /graphs/conc1/cGMP.PKG.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 56 0 0 1 simundump xplot /graphs/conc2/NO_GC.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 47 0 0 1 simundump xgraph /moregraphs/conc3 0 0 1000 0 0.0015738 0 simundump xgraph /moregraphs/conc4 0 0 1000 0 8.0731 0 simundump xplot /moregraphs/conc3/cGMP.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 52 0 0 1 simundump xplot /moregraphs/conc4/Gsub*.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 48 0 0 1 simundump xplot /moregraphs/conc4/PP2A_Gsub*.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 58 0 0 1 simundump xcoredraw /edit/draw 0 -2 16 -8 7 simundump xtree /edit/draw/tree 0 \ /kinetics/#[],/kinetics/#[]/#[],/kinetics/#[]/#[]/#[][TYPE!=proto],/kinetics/#[]/#[]/#[][TYPE!=linkinfo]/##[] \ "edit_elm.D ; drag_from_edit.w " auto 0.6 simundump xtext /file/notes 0 1 xtextload /file/notes \ "This model is based directly on paper by Shinya Kuroda,2001," \ "J.Neurosci., 21(15):5693-5702. This is a simulated model with the " \ "rates and other parameters obtained from various literature. " \ "This model also involves the cGMP dep PKG activity, and includes the" \ "PDE activity on cGMP." addmsg /kinetics/NObindGC /kinetics/GC REAC A B addmsg /kinetics/NObindGC /kinetics/NO REAC A B addmsg /kinetics/degradeNO /kinetics/NO REAC A B addmsg /kinetics/NObindGC /kinetics/NO_GC REAC B A addmsg /kinetics/NO_GC/kenz /kinetics/NO_GC REAC eA B addmsg /kinetics/NO_GC /kinetics/NO_GC/kenz ENZYME n addmsg /kinetics/GTP /kinetics/NO_GC/kenz SUBSTRATE n addmsg /kinetics/NO /kinetics/NObindGC SUBSTRATE n addmsg /kinetics/GC /kinetics/NObindGC SUBSTRATE n addmsg /kinetics/NO_GC /kinetics/NObindGC PRODUCT n addmsg /kinetics/NO /kinetics/degradeNO SUBSTRATE n addmsg /kinetics/NOdegrade /kinetics/degradeNO PRODUCT n addmsg /kinetics/degradeNO /kinetics/NOdegrade REAC B A addmsg /kinetics/NO_GC/kenz /kinetics/GTP REAC sA B addmsg /kinetics/NO_GC/kenz /kinetics/cGMP MM_PRD pA addmsg /kinetics/PDE/kenz /kinetics/cGMP REAC sA B addmsg /kinetics/cGMPbindPKG /kinetics/cGMP REAC A B addmsg /kinetics/PDE/kenz /kinetics/PDE REAC eA B addmsg /kinetics/PDE /kinetics/PDE/kenz ENZYME n addmsg /kinetics/cGMP /kinetics/PDE/kenz SUBSTRATE n addmsg /kinetics/cGMPbindPKG /kinetics/PKG REAC A B addmsg /kinetics/cGMP /kinetics/cGMPbindPKG SUBSTRATE n addmsg /kinetics/PKG /kinetics/cGMPbindPKG SUBSTRATE n addmsg /kinetics/cGMP.PKG /kinetics/cGMPbindPKG PRODUCT n addmsg /kinetics/cGMPbindPKG /kinetics/cGMP.PKG REAC B A addmsg /kinetics/cGMP.PKG/kenz /kinetics/cGMP.PKG REAC eA B addmsg /kinetics/cGMP.PKG /kinetics/cGMP.PKG/kenz ENZYME n addmsg /kinetics/Gsub /kinetics/cGMP.PKG/kenz SUBSTRATE n addmsg /kinetics/cGMP.PKG/kenz /kinetics/Gsub REAC sA B addmsg /kinetics/dephosphory /kinetics/Gsub REAC B A addmsg /kinetics/cGMP.PKG/kenz /kinetics/Gsub* MM_PRD pA addmsg /kinetics/PP2AbindGsub* /kinetics/Gsub* REAC A B addmsg /kinetics/dephosphory /kinetics/Gsub* REAC A B addmsg /kinetics/PP2AbindGsub* /kinetics/PP2A REAC A B addmsg /kinetics/PP2AbindGsub* /kinetics/PP2A_Gsub* REAC B A addmsg /kinetics/PP2A /kinetics/PP2AbindGsub* SUBSTRATE n addmsg /kinetics/Gsub* /kinetics/PP2AbindGsub* SUBSTRATE n addmsg /kinetics/PP2A_Gsub* /kinetics/PP2AbindGsub* PRODUCT n addmsg /kinetics/Gsub* /kinetics/dephosphory SUBSTRATE n addmsg /kinetics/Gsub /kinetics/dephosphory PRODUCT n addmsg /kinetics/PDE/kenz /kinetics/5prime_GMP MM_PRD pA addmsg /kinetics/NOdegrade /graphs/conc1/NOdegrade.Co PLOT Co *NOdegrade.Co *27 addmsg /kinetics/cGMP.PKG /graphs/conc1/cGMP.PKG.Co PLOT Co *cGMP.PKG.Co *56 addmsg /kinetics/NO_GC /graphs/conc2/NO_GC.Co PLOT Co *NO_GC.Co *47 addmsg /kinetics/cGMP /moregraphs/conc3/cGMP.Co PLOT Co *cGMP.Co *52 addmsg /kinetics/Gsub* /moregraphs/conc4/Gsub*.Co PLOT Co *Gsub*.Co *48 addmsg /kinetics/PP2A_Gsub* /moregraphs/conc4/PP2A_Gsub*.Co PLOT Co *PP2A_Gsub*.Co *58 enddump // End of dump call /kinetics/GC/notes LOAD \ "Guanylyl Cyclase ..." \ "Intracellular concentration is around 3 uM, as sGC is enrcihed" \ "in the Purkinje cells (Shinya Kuroda, personal corresspondence).." \ "Conc assumed on the basis of reported data in Ariano et al.," \ "1982, PNAS,79:297-300." call /kinetics/NO/notes LOAD \ "endogenous NO concentration is the course of signal transduction" \ "processes are around ~100 nM .." \ "(Varner et al., Nitric Oxide in the Nervous System, Academic Press," \ "pp:191-206)" call /kinetics/NO_GC/kenz/notes LOAD \ "Km - 45" \ "Vamx - 7.35" \ "" \ "Shinya Kuroda, J.Neurosci, 2001, 21(15):5693-5702." \ "" call /kinetics/NObindGC/notes LOAD \ "Kd 250 nM (Stone and Marletta, 1996).." \ "" \ "kf - 0.01" \ "kb - 0.0025" \ "" \ "Shinya Kuroda, J.Neurosci, 2001, 21(15):5693-5702 ..." call /kinetics/degradeNO/notes LOAD \ "degradation of NO ..." \ "kf - 0.673 / sec ...." \ "Shinya Kuroda, J.Neurosci, 2001, 21(15):5693-5702 " \ "" call /kinetics/GTP/notes LOAD \ "conc used from Bhalla and Iyengar,1999,Science, 283:381-387.." call /kinetics/PDE/notes LOAD \ "PhophoDiesterase ... Degrades cGMP to 5'GMP ..." \ "Conc Initially used from Kotera et al.,1997, Eur J Biochem," \ "249:434-442." call /kinetics/PDE/kenz/notes LOAD \ "Km - 2" \ "Vmax - 3.87" \ "Thru personal Correspondence with Shinya Kuroda..." \ "rates initially from Turko et al., 1998, Biochem J, 329," \ "505-510 .. " call /kinetics/PKG/notes LOAD \ "PKG inactive ... " \ "conc ~2.5 uM ..Lohmann et al., PNAS, 1981, 78:635-657. and" \ "Shinya Kuroda, personal correspondence ...." \ "" call /kinetics/cGMPbindPKG/notes LOAD \ "Kd - 0.05uM" \ "Shinya Kuroda, 2001, J.Neurosci., 21(15):5693-5702." call /kinetics/cGMP.PKG/kenz/notes LOAD \ "Km - 0.2" \ "Vmax - 0.72" \ "" \ "Shinya Kuroda, J.Neurosci, 2001, 21(15):5693-5702" \ "" call /kinetics/Gsub/notes LOAD \ "Conc from Detre et al., 1984, J Neurosci, 4:2843-2849." call /kinetics/PP2A/notes LOAD \ "conc from Mumby et al., 1985, J Biol Chem, 260:13763-13770." \ "" \ "" call /kinetics/PP2AbindGsub*/notes LOAD \ "Kd - 0.27 uM" \ "" \ "Shinya Kuroda, J.Neurosci, 2001, 21(15):5693-5702." call /kinetics/dephosphory/notes LOAD \ "kf - 0.0001/sec" \ "" \ "Shinya Kuroda, J.Neurosci, 2001, 21(15):5693-5702 ... " \ "and thru personal correspondence ..." call /kinetics/doqcsinfo/notes LOAD \ "This model of sGC is based on the paper by Kuroda S. et al. J Neurosci. (2001) 21(15):5693-702. This models features the activation of sGC by NO, synthesis of cGMP, activity of PKG and PP2A in the synapse. The rates and concentrations have been taken from published literature." complete_loading