-
Notifications
You must be signed in to change notification settings - Fork 0
/
Copy pathmorotti_et_al_mouse_barODEfile.m
374 lines (328 loc) · 15 KB
/
morotti_et_al_mouse_barODEfile.m
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
function ydot = morotti_et_al_mouse_barODEfile(t,y,pin)
% This module describes the beta-adrenergic signaling pathway in mouse
% ventricular myocyte, and this file was built upon the code developeded
% by Yang and Saucerman (2012).
%% Assign passed in params
LR=y(1);
LRG=y(2);
RG=y(3);
b1AR_S464=y(4);
b1AR_S301=y(5);
GsaGTPtot=y(6);
GsaGDP=y(7);
Gsby=y(8);
AC_GsaGTP=y(9);
PDEp=y(10);
cAMPtot=y(11);
RC_I=y(12);
RCcAMP_I=y(13);
RCcAMPcAMP_I=y(14);
RcAMPcAMP_I=y(15);
PKACI=y(16);
PKACI_PKI=y(17);
RC_II=y(18);
RCcAMP_II=y(19);
RCcAMPcAMP_II=y(20);
RcAMPcAMP_II=y(21);
PKACII=y(22);
PKACII_PKI=y(23);
I1p_PP1=y(24);
I1ptot=y(25);
PLBp=y(26); % output
PLMp=y(27); % output
LCCap=y(28); % output
LCCbp=y(29); % output
RyRp=y(30); % output
TnIp=y(31); % output
KS79=y(32);
KS80=y(33);
KSp=y(34); % output -> 0
CFTRp=y(35); % output -> 0
KURp=y(36); % output
%% Drug Concentrations
ISO = pin(1); % (uM) isoproterenol concentration - Ltot
FSK = 0; % (uM) forskolin concentration
IBMX = 0; % (uM) IBMX concentration
%% -------- SIGNALING MODEL -----------
ydot = zeros(size(y));
%% b-AR module
b1ARtot = 0.00528; % (uM) total b1-AR protein % MOUSE
%b1ARtot=0.028; % RABBIT
kf_LR = 1; % (1/[uM ms]) forward rate for ISO binding to b1AR
kr_LR = 0.285; % (1/ms) reverse rate for ISO binding to b1AR
kf_LRG = 1; % (1/[uM ms]) forward rate for ISO:b1AR association with Gs
kr_LRG = 0.062; % (1/ms) reverse rate for ISO:b1AR association with Gs
kf_RG = 1; % (1/[uM ms]) forward rate for b1AR association with Gs
kr_RG = 33; % (1/ms) reverse rate for b1AR association with Gs
Gstot = 3.83; % (uM) total Gs protein
k_G_act = 16e-3; % (1/ms) rate constant for Gs activation
k_G_hyd = 0.8e-3; % (1/ms) rate constant for G-protein hydrolysis
k_G_reassoc = 1.21; % (1/[uM ms]) rate constant for G-protein reassociation
kf_bARK = 1.1e-6; % (1/[uM ms]) forward rate for b1AR phosphorylation by b1ARK
kr_bARK = 2.2e-6; % (1/ms) reverse rate for b1AR phosphorylation by b1ARK
kf_PKA = 3.6e-6; % (1/[uM ms]) forward rate for b1AR phosphorylation by PKA
kr_PKA = 2.2e-6; % (1/ms) reverse rate for b1AR phosphorylation by PKA
b1ARact = b1ARtot - b1AR_S464 - b1AR_S301;
b1AR = b1ARact - LR - LRG - RG;
Gs = Gstot - LRG - RG - Gsby;
dLR = kf_LR*ISO*b1AR - kr_LR*LR + kr_LRG*LRG - kf_LRG*LR*Gs;
dLRG = kf_LRG*LR*Gs - kr_LRG*LRG - k_G_act*LRG;
dRG = kf_RG*b1AR*Gs - kr_RG*RG - k_G_act*RG;
bARK_desens = kf_bARK*(LR+LRG);
bARK_resens = kr_bARK*b1AR_S464;
PKA_desens = kf_PKA*PKACI*b1ARact;
PKA_resens = kr_PKA*b1AR_S301;
db1AR_S464 = bARK_desens - bARK_resens; % ydot(5)
db1AR_S301 = PKA_desens - PKA_resens; % ydot(6)
G_act = k_G_act*(RG+LRG);
G_hyd = k_G_hyd*GsaGTPtot;
G_reassoc = k_G_reassoc*GsaGDP*Gsby;
dGsaGTPtot = G_act - G_hyd; % ydot(7)
dGsaGDP = G_hyd - G_reassoc; % ydot(8)
dGsby = G_act - G_reassoc; % ydot(9)
% end b-AR module
%% cAMP module
ACtot = 70.57e-3; % (uM) total adenylyl cyclase % MOUSE
% ACtot=47e-3; % RABBIT
ATP = 5e3; % (uM) total ATP
k_AC_basal = 0.2e-3; % (1/ms) basal cAMP generation rate by AC
Km_AC_basal = 1.03e3; % (uM) basal AC affinity for ATP
Kd_AC_Gsa = 0.4; % (uM) Kd for AC association with Gsa
kf_AC_Gsa = 1; % (1/[uM ms]) forward rate for AC association with Gsa
kr_AC_Gsa = Kd_AC_Gsa; % (1/ms) reverse rate for AC association with Gsa
k_AC_Gsa = 8.5e-3; % (1/ms) basal cAMP generation rate by AC:Gsa
Km_AC_Gsa = 315.0; % (uM) AC:Gsa affinity for ATP
Kd_AC_FSK = 44.0; % (uM) Kd for FSK binding to AC
k_AC_FSK = 7.3e-3; % (1/ms) basal cAMP generation rate by AC:FSK
Km_AC_FSK = 860.0; % (uM) AC:FSK affinity for ATP
PDEtot = 22.85e-3; % (uM) total phosphodiesterase
k_cAMP_PDE = 5e-3; % (1/ms) cAMP hydrolysis rate by PDE
k_cAMP_PDEp = 2*k_cAMP_PDE; % (1/ms) cAMP hydrolysis rate by phosphorylated PDE
Km_PDE_cAMP = 1.3; % (uM) PDE affinity for cAMP
Kd_PDE_IBMX = 30.0; % (uM) Kd_R2cAMP_C for IBMX binding to PDE
k_PKA_PDE = 7.5e-3; % (1/ms) rate constant for PDE phosphorylation by type 1 PKA
k_PP_PDE = 1.5e-3; % (1/ms) rate constant for PDE dephosphorylation by phosphatases
cAMP = cAMPtot - (RCcAMP_I+2*RCcAMPcAMP_I+2*RcAMPcAMP_I) - (RCcAMP_II+2*RCcAMPcAMP_II+2*RcAMPcAMP_II);
AC = ACtot-AC_GsaGTP;
GsaGTP = GsaGTPtot - AC_GsaGTP;
dAC_GsaGTP = kf_AC_Gsa*GsaGTP*AC - kr_AC_Gsa*AC_GsaGTP;
AC_FSK = FSK*AC/Kd_AC_FSK;
AC_ACT_BASAL = k_AC_basal*AC*ATP/(Km_AC_basal+ATP);
AC_ACT_GSA = k_AC_Gsa*AC_GsaGTP*ATP/(Km_AC_Gsa+ATP);
AC_ACT_FSK = k_AC_FSK*AC_FSK*ATP/(Km_AC_FSK+ATP);
PDE_IBMX = PDEtot*IBMX/Kd_PDE_IBMX;
PDE = PDEtot - PDE_IBMX - PDEp;
dPDEp = k_PKA_PDE*PKACII*PDE - k_PP_PDE*PDEp;
PDE_ACT = k_cAMP_PDE*PDE*cAMP/(Km_PDE_cAMP+cAMP) + k_cAMP_PDEp*PDEp*cAMP/(Km_PDE_cAMP+cAMP);
dcAMPtot = AC_ACT_BASAL + AC_ACT_GSA + AC_ACT_FSK - PDE_ACT; % ydot(15)
% end cAMP module
%% PKA module
PKItot = 0.18; % (uM) total PKI
kf_RC_cAMP = 1; % (1/[uM ms]) Kd for PKA RC binding to cAMP
kf_RCcAMP_cAMP = 1; % (1/[uM ms]) Kd for PKA RC:cAMP binding to cAMP
kf_RcAMPcAMP_C = 4.375; % (1/[uM ms]) Kd for PKA R:cAMPcAMP binding to C
kf_PKA_PKI = 1; % (1/[uM ms]) Ki for PKA inhibition by PKI
kr_RC_cAMP = 1.64; % (1/ms) Kd for PKA RC binding to cAMP
kr_RCcAMP_cAMP = 9.14; % (1/ms) Kd for PKA RC:cAMP binding to cAMP
kr_RcAMPcAMP_C = 1; % (1/ms) Kd for PKA R:cAMPcAMP binding to C
kr_PKA_PKI = 2e-4; % (1/ms) Ki for PKA inhibition by PKI
epsilon = 10; % (-) AKAP-mediated scaling factor
PKI = PKItot - PKACI_PKI - PKACII_PKI;
dRC_I = - kf_RC_cAMP*RC_I*cAMP + kr_RC_cAMP*RCcAMP_I;
dRCcAMP_I = - kr_RC_cAMP*RCcAMP_I + kf_RC_cAMP*RC_I*cAMP - kf_RCcAMP_cAMP*RCcAMP_I*cAMP + kr_RCcAMP_cAMP*RCcAMPcAMP_I;
dRCcAMPcAMP_I = - kr_RCcAMP_cAMP*RCcAMPcAMP_I + kf_RCcAMP_cAMP*RCcAMP_I*cAMP - kf_RcAMPcAMP_C*RCcAMPcAMP_I + kr_RcAMPcAMP_C*RcAMPcAMP_I*PKACI;
dRcAMPcAMP_I = - kr_RcAMPcAMP_C*RcAMPcAMP_I*PKACI + kf_RcAMPcAMP_C*RCcAMPcAMP_I;
dPKACI = - kr_RcAMPcAMP_C*RcAMPcAMP_I*PKACI + kf_RcAMPcAMP_C*RCcAMPcAMP_I - kf_PKA_PKI*PKACI*PKI + kr_PKA_PKI*PKACI_PKI; % ydot(17)
dPKACI_PKI = - kr_PKA_PKI*PKACI_PKI + kf_PKA_PKI*PKACI*PKI;
dRC_II = - kf_RC_cAMP*RC_II*cAMP + kr_RC_cAMP*RCcAMP_II;
dRCcAMP_II = - kr_RC_cAMP*RCcAMP_II + kf_RC_cAMP*RC_II*cAMP - kf_RCcAMP_cAMP*RCcAMP_II*cAMP + kr_RCcAMP_cAMP*RCcAMPcAMP_II;
dRCcAMPcAMP_II = - kr_RCcAMP_cAMP*RCcAMPcAMP_II + kf_RCcAMP_cAMP*RCcAMP_II*cAMP - kf_RcAMPcAMP_C*RCcAMPcAMP_II + kr_RcAMPcAMP_C*RcAMPcAMP_II*PKACII;
dRcAMPcAMP_II = - kr_RcAMPcAMP_C*RcAMPcAMP_II*PKACII + kf_RcAMPcAMP_C*RCcAMPcAMP_II;
dPKACII = - kr_RcAMPcAMP_C*RcAMPcAMP_II*PKACII + kf_RcAMPcAMP_C*RCcAMPcAMP_II - kf_PKA_PKI*PKACII*PKI + kr_PKA_PKI*PKACII_PKI; % ydot(18)
dPKACII_PKI = - kr_PKA_PKI*PKACII_PKI + kf_PKA_PKI*PKACII*PKI;
% end PKA module
%% I-1/PP1 module
PP1tot = pin(8); % PP1tot = 0.89; % (uM) total phosphatase 1
I1tot = 0.3; % (uM) total inhibitor 1
k_PKA_I1 = 60e-3; % (1/ms) rate constant for I-1 phosphorylation by type 1 PKA
Km_PKA_I1 = 1.0; % (uM) Km for I-1 phosphorylation by type 1 PKA
Vmax_PP2A_I1 = 14.0e-3; % (uM/ms) Vmax for I-1 dephosphorylation by PP2A
Km_PP2A_I1 = 1.0; % (uM) Km for I-1 dephosphorylation by PP2A
Ki_PP1_I1 = 1.0e-3; % (uM) Ki for PP1 inhibition by I-1
kf_PP1_I1 = 1; % (uM) Ki for PP1 inhibition by I-1
kr_PP1_I1 = Ki_PP1_I1; % (uM) Ki for PP1 inhibition by I-1
I1 = I1tot - I1ptot;
PP1 = PP1tot - I1p_PP1;
I1p = I1ptot - I1p_PP1;
I1_phosph = k_PKA_I1*PKACI*I1/(Km_PKA_I1+I1);
I1_dephosph = Vmax_PP2A_I1*I1ptot/(Km_PP2A_I1+I1ptot);
dI1p_PP1 = kf_PP1_I1*PP1*I1p - kr_PP1_I1*I1p_PP1;
dI1ptot = I1_phosph - I1_dephosph; % ydot(20)
% end I-1/PP1 module
%% PLB module
PLBtot = pin(4); %p(41) = PLBtot; % PLBtot [uM]
k_PKA_PLB = 54e-3; %p(44) = 54; % k_pka_plb [1/ms]
Km_PKA_PLB = 21; %p(45) = 21; % Km_pka_plb [uM]
k_PP1_PLB = 8.5e-3; %p(46) = 8.5; % k_pp1_plb [1/ms]
Km_PP1_PLB = 7.0; %p(47) = 7.0; % Km_pp1_plb [uM]
PLB = PLBtot - PLBp;
PLB_phosph = k_PKA_PLB*PKACI*PLB/(Km_PKA_PLB+PLB);
PLB_dephosph = k_PP1_PLB*PP1*PLBp/(Km_PP1_PLB+PLBp);
dPLBp = PLB_phosph - PLB_dephosph; % ydot(19)
% end PLB module
%% PLM module (included 09/18/12) MOUSE
PLMtot = pin(10); % p(102) = PLMtot; % PLMtot [uM]
k_PKA_PLM = 54e-3; % p(103) = 54; % k_pka_plb [1/ms]
Km_PKA_PLM = 21; % p(104) = 21; % Km_pka_plb [uM]
k_PP1_PLM = 8.5e-3; % p(105) = 8.5; % k_pp1_plb [1/ms]
Km_PP1_PLM = 7.0; % p(106) = 7.0; % Km_pp1_plb [uM]
PLM = PLMtot - PLMp;
PLM_phosph = k_PKA_PLM*PKACI*PLM/(Km_PKA_PLM+PLM);
PLM_dephosph = k_PP1_PLM*PP1*PLMp/(Km_PP1_PLM+PLMp);
dPLMp = PLM_phosph - PLM_dephosph; % ydot(32)
% end PLM module
%% LCC module
PKAIItot = 0.059; % (uM) total type 2 PKA % MOUSE
% PKAIItot=0.084; % RABBIT
LCCtot = pin(2); %p(53) = LCCtot; % LCCtot [uM]
PKACII_LCCtot = 0.025; %p(54) = 0.025; % PKAIIlcctot [uM]
PP1_LCC = 0.025; %p(55) = 0.025; % PP1lcctot [uM]
PP2A_LCC = 0.025; %p(56) = 0.025; % PP2Alcctot [uM]
k_PKA_LCC = 54e-3; %p(57) = 54; % k_pka_lcc [1/ms]
Km_PKA_LCC = 21; %p(58) = 21;%*1.6; % Km_pka_lcc [uM]
k_PP1_LCC = 8.52e-3; %p(59) = 8.52; % k_pp1_lcc [1/ms] RABBIT, MOUSE
%p(59) = 8.5; % k_pp1_lcc [1/sec] RAT
Km_PP1_LCC = 3; %p(60) = 3; % Km_pp1_lcc [uM]
k_PP2A_LCC = 10.1e-3; %p(61) = 10.1; % k_pp2a_lcc [1/ms]
Km_PP2A_LCC = 3; %p(62) = 3; % Km_pp2a_lcc [uM]
PKACII_LCC = (PKACII_LCCtot/PKAIItot)*PKACII;
LCCa = LCCtot - LCCap;
LCCa_phosph = epsilon*k_PKA_LCC*PKACII_LCC*LCCa/(Km_PKA_LCC+epsilon*LCCa);
LCCa_dephosph = epsilon*k_PP2A_LCC*PP2A_LCC*LCCap/(Km_PP2A_LCC+epsilon*LCCap);
dLCCap = LCCa_phosph - LCCa_dephosph; % ydot(23)
LCCb = LCCtot - LCCbp;
LCCb_phosph = epsilon*k_PKA_LCC*PKACII_LCC*LCCb/(Km_PKA_LCC+epsilon*LCCb);
LCCb_dephosph = epsilon*k_PP1_LCC*PP1_LCC*LCCbp/(Km_PP1_LCC+epsilon*LCCbp);
dLCCbp = LCCb_phosph - LCCb_dephosph; % ydot(24)
% end LCC module
%% RyR module (not included in Yang-Saucerman)
RyRtot = pin(3); %p(63) = RyRtot; % RyRtot [uM]
PKAIIryrtot = 0.034; %p(64) = 0.034; % PKAIIryrtot [uM]
PP1ryr = 0.034; %p(65) = 0.034; % PP1ryr [uM]
PP2Aryr = 0.034; %p(66) = 0.034; % PP2Aryr [uM]
kcat_pka_ryr = 54e-3; %p(67) = 54; % kcat_pka_ryr [1/ms]
Km_pka_ryr = 21; %p(68) = 21; % Km_pka_ryr [uM]
kcat_pp1_ryr = 8.52e-3; %p(69) = 8.52; % kcat_pp1_ryr [1/ms]
Km_pp1_ryr = 7; %p(70) = 7; % Km_pp1_ryr [uM]
kcat_pp2a_ryr = 10.1e-3; %p(71) = 10.1; % kcat_pp2a_ryr [1/ms]
Km_pp2a_ryr = 4.1; %p(72) = 4.1; % Km_pp2a_ryr [uM]
PKACryr = (PKAIIryrtot/PKAIItot)*PKACII;
RyR = RyRtot-RyRp;
RyRPHOSPH = epsilon*kcat_pka_ryr*PKACryr*RyR/(Km_pka_ryr+epsilon*RyR);
RyRDEPHOSPH1 = epsilon*kcat_pp1_ryr*PP1ryr*RyRp/(Km_pp1_ryr+epsilon*RyRp);
RyRDEPHOSPH2A = epsilon*kcat_pp2a_ryr*PP2Aryr*RyRp/(Km_pp2a_ryr+epsilon*RyRp);
dRyRp = RyRPHOSPH-RyRDEPHOSPH1-RyRDEPHOSPH2A; % ydot(25)
% end RyR module
%% TnI module
TnItot = pin(5); %p(73) = TnItot; % TnItot [uM]
PP2A_TnI = 0.67; % PP2Atni [uM]
k_PKA_TnI = 54e-3; % kcat_pka_tni [1/ms]
Km_PKA_TnI = 21; % Km_pka_tni [uM]
k_PP2A_TnI = 10.1e-3; % kcat_pp2a_tni [1/ms]
Km_PP2A_TnI = 4.1; % Km_pp2a_tni [uM]
TnI = TnItot - TnIp;
TnI_phosph = k_PKA_TnI*PKACI*TnI/(Km_PKA_TnI+TnI);
TnI_dephosph = k_PP2A_TnI*PP2A_TnI*TnIp/(Km_PP2A_TnI+TnIp);
dTnIp = TnI_phosph - TnI_dephosph; % ydot(26)
% end TnI module
%% Iks module (not present in mouse)
IKstot = pin(6);
% p(79) = IKstot; % Iks_tot [uM]
% p(80) = 0.025; % Yotiao_tot [uM]
% p(81) = 0.1e-3; % K_yotiao [uM] ** apply G589D mutation here **
% p(82) = 0.025; % PKAII_ikstot [uM]
% p(83) = 0.025; % PP1_ikstot [uM]
% p(84) = 54; % k_pka_iks [1/sec]
% p(85) = 21; % Km_pka_iks [uM]
% p(86) = 8.52; % k_pp1_iks [1/sec]
% p(87) = 7; % Km_pp1_iks [uM]
%
% IksYot = y(27)*y(28)/p(81); % [uM]
% ydot(27) = p(79) - IksYot - y(27); % [uM]
% ydot(28) = p(80) - IksYot - y(28); % [uM]
% PKACiks = (IksYot/p(79))*(p(82)/p(34))*y(18);
% PP1iks = (IksYot/p(79))*p(83);
% Iks = p(79)-y(29);
% IKS_PHOSPH = p(40)*p(84)*PKACiks*Iks/(p(85)+p(40)*Iks);
% IKS_DEPHOSPH = p(40)*p(86)*PP1iks*y(29)/(p(87)+p(40)*y(29));
% ydot(29) = IKS_PHOSPH-IKS_DEPHOSPH;
% end Iks module
dKS79 = 0; % ydot(27) not ODE
dKS80 = 0; % ydot(28) not ODE
dKSp = 0; % ydot(29)
%% CFTR module (included 04/30/10)
ICFTRtot = pin(7); % p(88) = ICFTRtot; % ICFTR_tot [uM]
% PKAII_CFTRtot = 0.025; %p(89) = 0.025; % PKAII_CFTRtot [uM]
% PP1_CFTRtot = 0.025; %p(90) = 0.025; % PP1_CFTRtot [uM]
% k_pka_CFTR = 54e-3; %p(91) = 54; % k_pka_CFTR [1/ms]
% Km_pka_CFTR = 8.5; %p(92) = 8.5; % Km_pka_CFTR [uM]
% k_pp1_CFTR = 8.52e-3; %p(93) = 8.52; % k_pp1_CFTR [1/ms]
% Km_pp1_CFTR = 7; %p(94) = 7; % Km_pp1_CFTR [uM]
%
% CFTRn = ICFTRtot - CFTRp; % Non-phos = tot - phos
% PKAC_CFTR = (PKAII_CFTRtot/PKAIItot)*PKACII; % (PKACFTRtot/PKAIItot)*PKAIIact
% CFTRphos = epsilon*CFTRn*PKAC_CFTR*k_pka_CFTR/(Km_pka_CFTR+epsilon*CFTRn);
% CFTRdephos = PP1_CFTRtot*k_pp1_CFTR*epsilon*CFTRp/(Km_pp1_CFTR + epsilon*CFTRp);
dCFTRp = 0; %CFTRphos - CFTRdephos; % ydot(30)
% end CFTR module
%% Ikur module (included 04/10/12) MOUSE
IKurtot = pin(9);% p(95) = IKurtot; % Ikur_tot [uM]
PKAII_KURtot = 0.025; % p (96) = 0.025; % PKAII_KURtot [uM]
PP1_KURtot = 0.025; % p(97) = 0.025; % PP1_KURtot [uM]
k_pka_KUR = 54e-3; % p(98) = 54; % k_pka_KUR [1/ms]
Km_pka_KUR = 21; % p(99) = 21; % Km_pka_KUR [uM]
k_pp1_KUR = 8.52e-3; % p(100) = 8.52; % k_pp1_KUR [1/ms]
Km_pp1_KUR = 7; % p(101) = 7; % Km_pp1_KUR [uM]
KURn = IKurtot - KURp; % Non-phos = tot - phos
PKAC_KUR = (PKAII_KURtot/PKAIItot)*PKACII; % (PKA_KURtot/PKAIItot)*PKAIIact
KURphos = epsilon*KURn*PKAC_KUR*k_pka_KUR/(Km_pka_KUR+epsilon*KURn);
KURdephos = PP1_KURtot*k_pp1_KUR*epsilon*KURp/(Km_pp1_KUR+epsilon*KURp);
dKURp = KURphos - KURdephos; % ydot(31)
% end Ikur module
%% ydot
ydot(1)=dLR;
ydot(2)=dLRG;
ydot(3)=dRG;
ydot(4)=db1AR_S464;
ydot(5)=db1AR_S301;
ydot(6)=dGsaGTPtot;
ydot(7)=dGsaGDP;
ydot(8)=dGsby;
ydot(9)=dAC_GsaGTP;
ydot(10)=dPDEp;
ydot(11)=dcAMPtot;
ydot(12)=dRC_I;
ydot(13)=dRCcAMP_I;
ydot(14)=dRCcAMPcAMP_I;
ydot(15)=dRcAMPcAMP_I;
ydot(16)=dPKACI;
ydot(17)=dPKACI_PKI;
ydot(18)=dRC_II;
ydot(19)=dRCcAMP_II;
ydot(20)=dRCcAMPcAMP_II;
ydot(21)=dRcAMPcAMP_II;
ydot(22)=dPKACII;
ydot(23)=dPKACII_PKI;
ydot(24)=dI1p_PP1; % output CaMKII
ydot(25)=dI1ptot;
ydot(26)=dPLBp; % output
ydot(27)=dPLMp; % output
ydot(28)=dLCCap; % output
ydot(29)=dLCCbp; % output
ydot(30)=dRyRp; % output
ydot(31)=dTnIp; % output
ydot(32)=dKS79;
ydot(33)=dKS80;
ydot(34)=dKSp; % output -> 0
ydot(35)=dCFTRp; % output -> 0
ydot(36)=dKURp; % output