Chaste Commit::baa90ac2819b962188b7562f2326be23c47859a7
CorriasBuistICCModified.cpp
1/*
2
3Copyright (c) 2005-2024, University of Oxford.
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9
10This file is part of Chaste.
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12Redistribution and use in source and binary forms, with or without
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23THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS "AS IS"
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33
34*/
35
36#include "CorriasBuistICCModified.hpp"
37#include <cmath>
38#include <cassert>
39#include <memory>
40#include "Exception.hpp"
41#include "OdeSystemInformation.hpp"
42#include "HeartConfig.hpp"
43
44 CorriasBuistICCModified::CorriasBuistICCModified(boost::shared_ptr<AbstractIvpOdeSolver> pSolver, boost::shared_ptr<AbstractStimulusFunction> pIntracellularStimulus)
46 pSolver,
47 18,//reduced by 3 from original
48 0,
49 pIntracellularStimulus)
50 {
51
54 mIP3Concentration = 0.0006;
56 mScaleFactorCarbonMonoxide = 1.0; //initialise to 1 --> no effect
57 //IP3 = 0.00065;// mM *** no longer used ***
58
60 //Constants
62
63 /* Concentrations */
64 Ca_o = 2.5 ;// mM
65 Cl_o =134.0 ;// mM
66 K_o =7.0 ;// mM
67 Na_o =137.0 ;// mM
68
69 /* Nernst parameters */
70 R = 8314.4 ;// pJ/nmol/K
71 T = 310.0 ;// degK
72 F = 96484.6;// nC/nmol
73 FoRT = 0.03743;// 1/mV
74 RToF = 26.7137;// mV
75
76 Cm = 25.0*1e-6;// 25 pF --> microF
77
79 Asurf = Asurf_in_cm_square / 0.01;//cm2 --> mm2
80
81 Cl_i = 88.0 ;// mM
82 K_i = 120.0 ;// mM
83 Na_i = 30.0 ;// mM
84 P_cyto = 0.7;// dim
85 Vol = 1.0e-6 ;// mm3
86 fc = 0.01 ;// dim
87 fe = 0.01 ;// dim
88 fm = 0.0003 ;// dim
89 Q10Ca = 2.1;// dim
90 Q10K = 1.5;// dim
91 Q10Na = 2.45 ;// dim
92 T_exp = 297.0 ;// degK
93
94 G_max_BK = 23.0 * 1e-6 / Asurf;// 9.2e-3 mS/mm2 (23.0 nS) * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
95 G_max_CaCl = 10.1 * 1e-6 / Asurf; //4.04e-3 mS/mm2 (10.1 nS) * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
96 G_max_ERG = 2.5 * 1e-6 / Asurf; //1.0e-3 mS/mm2 ( 2.5 nS) * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
97 G_max_Ltype = 2.0 * 1e-6 / Asurf;//0.8e-3 mS/mm2 ( 2.0 nS) * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
98 G_max_NSCC = 12.15 * 1e-6 / Asurf;//4.86e-3 mS/mm2 (12.15nS) * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
99 G_max_Na = 20.0 * 1e-6 / Asurf;//8.0e-3 mS/mm2 (20.0 nS) * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
100 G_max_VDDR = 3.0 * 1e-6 / Asurf;//1.2e-3 mS/mm2 ( 3.0 nS) * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
101 G_max_bk = 0.15 * 1e-6 / Asurf;//0.06e-3 mS/mm2 (0.15 nS) * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
102 G_max_kv11 = 6.3 * 1e-6 / Asurf;//2.52e-3 mS/mm2 ( 6.3 nS) * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
103
104 J_max_PMCA = 0.088464e-3 ;// mM/ms (mM/s) * 1/1000 (s/ms) = mM/ms
105 J_max_PMCA_PU = 0.33e-3;// mM/ms (mM/s) * 1/1000 (s/ms) = mM/ms
106 J_ERleak = 1.666667e-3 ;// 1/ms (1/s) * 1/1000 (ms/s) = 1/ms
107 J_max_leak = 0.0;// 1/ms (1/s) * 1/1000 (ms/s) = 1/ms
108 Jmax_IP3 = 50000.0e-3 ;// 1/ms (1/s) * 1/1000 (ms/s) = 1/ms
109 Jmax_NaCa = 0.05e-3;// mM/ms (mM/s) * 1/1000 (s/ms) = mM/ms
110 Jmax_serca = 1.8333e-3 ;// mM/ms (mM/s) * 1/1000 (s/ms) = mM/ms
111 Jmax_uni = 5000.0e-3 ;// 1/ms (1/s) * 1/1000 (ms/s) = 1/ms
112
113 NaPerm_o_Kperm = 1.056075 ;// dim
114 L = 50.0 ;// dim
115 P_ER = 0.1;// dim
116 P_PU = 0.001 ;// dim
117 P_mito = 0.12871;// dim
118 b = 0.5;// dim
119 na = 2.8;// dim
120
121 K_Ca = 0.003 ;// mM
122 K_Na = 9.4;// mM
123 K_act = 0.00038;// mM
124 K_trans = 0.006 ;// mM
125 k_serca = 0.00042;// mM
126 conc = 0.001 ;// mM
127 d_ACT = 0.001 ;// mM
128 d_IP3 = 0.00025;// mM
129 d_INH = 0.0014 ;// mM
130
131 tau_d_CaCl = 0.03e3 ;// ms(s) * 1000 (ms/s) = ms
132 tau_d_NSCC = 0.35e3 ;// ms(s) * 1000 (ms/s) = ms
133 tauh = 4.0e3 ;// ms(s ) * 1000 (ms/s) = ms
134
135 deltaPsi_B = 50.0 ;// mV
136 deltaPsi_star = 91.0 ;// mV
137 deltaPsi = 164.000044 ;// mV
138
140 //Calculated constants
142
143 /* Volumes */
144 V_cyto = Vol*P_cyto;
145 V_MITO = Vol*P_mito;
146 V_PU = Vol*P_PU;
147 V_ER = Vol*P_ER;
148
149 /* Temperature corrections */
150 T_correction_Ca = pow(Q10Ca, (T-T_exp)/10.0);
151 T_correction_K = pow(Q10K, (T-T_exp)/10.0);
152 T_correction_Na = pow(Q10Na, (T-T_exp)/10.0);
153 T_correction_BK = 1.1*(T-T_exp)*1e-6/Asurf; //(nS) * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
154
155 /* Nernst potentials */
156 E_Na = RToF*log(Na_o/Na_i);
157 E_K = RToF*log(K_o/K_i);
158 E_Cl = RToF*log(Cl_i/Cl_o);
160
161 /* Activation gate time constants s->ms */
162 tau_d_ERG = T_correction_K*0.003*1000.0;
163 tau_d_Ltype = T_correction_Ca*0.001*1000.0;
164 tau_d_Na = T_correction_Na*0.003*1000.0;
165 tau_d_VDDR = T_correction_Ca*0.006*1000.0;
166 tau_d_kv11 = T_correction_K*0.005*1000.0;
167
168 /* Inactivation gate time constants s->ms */
169 tau_f_Ltype = T_correction_Ca*0.086*1000.0;
170 tau_f_Na = T_correction_Na*0.0016*1000.0;
171 tau_f_VDDR = T_correction_Ca*0.04*1000.0;
172 tau_f_ca_Ltype = T_correction_Ca*0.002*1000.0;
173 tau_f_kv11 = T_correction_K*0.005*1000.0;
174
175 /* Speed ups */
178
179
180 Init();
181
182 }
183
187
190
192 {
193 mScaleFactorSerca = scaleFactor;
194 }
195
197 {
198 mFractionOfVDDRInPU = fraction;
199 }
200
202 {
203 mIP3Concentration = concentration;
204 }
205
207 {
208 mScaleFactorCarbonMonoxide = scaleFactor;
209 }
210
215
216 double CorriasBuistICCModified::GetIIonic(const std::vector<double>* pStateVariables)
217 {
218 if (!pStateVariables) pStateVariables = &rGetStateVariables();
219 const std::vector<double>& rY = *pStateVariables;
220
221 // index 0: Vm (mV)
222 // index 1: Ca_i (mM)
223 // index 2: Ca_ER (mM)
224 // index 3: Ca_PU (mM)
225 // index 4: Ca_m (mM)
226 // index 5: h (dim)
227 // index 6: d_CaCl (dim)
228 // index 7: d_ERG (dim)
229 // index 8: d_Ltype (dim)
230 // index 9: d_NSCC (dim)
231 // index 10: d_Na (dim)
232 // index 11: d_VDDR (dim)
233 // index 12: d_kv11 (dim)
234 // index 13: f_Ltype (dim)
235 // index 14: f_Na (dim)
236 // index 15: f_VDDR (dim)
237 // index 16: f_ca_Ltype (dim)
238 // index 17: f_kv11 (dim)
239
240 double E_Ca = 0.5*RToF*log(Ca_o/rY[1]);
241 /* --- INa --- */
242 double I_Na = G_max_Na*rY[14]*rY[10]*(rY[0]-E_Na);
243 /* --- ILtype --- */
244 double I_Ltype = G_max_Ltype*rY[13]*rY[8]*rY[16]*(rY[0]-E_Ca);
245 /* --- IVDDR --- */
246 double I_VDDR = G_max_VDDR*rY[15]*rY[11]*(rY[0]-E_Ca);
247 /* --- IKv1.1 --- */
248 double I_kv11 = mScaleFactorCarbonMonoxide*G_max_kv11*rY[17]*rY[12]*(rY[0]-E_K);
249 /* --- IERG --- */
250 double I_ERG = mScaleFactorCarbonMonoxide*G_max_ERG*rY[7]*(rY[0]-E_K);
251 /* --- IBK --- */
252 double d_BK = 1.0/(1.0+((exp(rY[0]/-17.0))/((rY[1]/0.001)*(rY[1]/0.001))));
253 double I_BK = (G_max_BK+T_correction_BK)*d_BK*(rY[0]-E_K);
254 /* --- IKb --- */
255 double I_bk = mScaleFactorCarbonMonoxide*G_max_bk*(rY[0]-E_K);
256 /* --- ICaCL --- */
257 double I_CaCl = G_max_CaCl*rY[6]*(rY[0]-E_Cl);
258 /* --- INSCC --- */
259 double I_NSCC = G_max_NSCC*rY[9]*(rY[0]-E_NSCC);
260 /* --- JpmCa --- */
261 double J_PMCA = J_max_PMCA*1.0/(1.0+(0.000298/rY[1]));
262
263 //i_ionic_in microA/mm2
264 double i_ionic = (I_Na+I_Ltype+I_VDDR+I_kv11+I_ERG+I_BK+I_CaCl+I_NSCC+I_bk+(J_PMCA*2.0*F*V_cyto/Asurf));
265 assert(!std::isnan(i_ionic));
269 return i_ionic / 0.01;
270 }
271
272 void CorriasBuistICCModified::EvaluateYDerivatives(double time, const std::vector<double>& rY, std::vector<double>& rDY)
273 {
274 // index 0: Vm (mV)
275 // index 1: Ca_i (mM)
276 // index 2: Ca_ER (mM)
277 // index 3: Ca_PU (mM)
278 // index 4: Ca_m (mM)
279 // index 5: h (dim)
280 // index 6: d_CaCl (dim)
281 // index 7: d_ERG (dim)
282 // index 8: d_Ltype (dim)
283 // index 9: d_NSCC (dim)
284 // index 10: d_Na (dim)
285 // index 11: d_VDDR (dim)
286 // index 12: d_kv11 (dim)
287 // index 13: f_Ltype (dim)
288 // index 14: f_Na (dim)
289 // index 15: f_VDDR (dim)
290 // index 16: f_ca_Ltype (dim)
291 // index 17: f_kv11 (dim)
292
293 /* ----------------- */
294 /* Membrane currents */
295 /* ----------------- */
296
297 double E_Ca = 0.5*RToF*log(Ca_o/rY[1]);
298
299 /* --- INa --- */
300 double d_inf_Na = 1.0/(1.0+exp((rY[0]+47.0)/-4.8));
301 double f_inf_Na = 1.0/(1.0+exp((rY[0]+78.0)/7.0));
302 double I_Na = G_max_Na*rY[14]*rY[10]*(rY[0]-E_Na);
303
304 /* --- ILtype --- */
305 double d_inf_Ltype = 1.0/(1.0+exp((rY[0]+17.0)/-4.3));
306 double f_inf_Ltype = 1.0/(1.0+exp((rY[0]+43.0)/8.9));
307 double f_ca_inf_Ltype = 1.0-1.0/(1.0+exp((rY[1]-0.0001-0.000214)/-0.0000131));
308 double I_Ltype = G_max_Ltype*rY[13]*rY[8]*rY[16]*(rY[0]-E_Ca);
309
310 /* --- IVDDR --- */
311 double d_inf_VDDR = 1.0/(1.0+exp((rY[0]+26.0)/-6.0));
312 double f_inf_VDDR = 1.0/(1.0+exp((rY[0]+66.0)/6.0));
313 double I_VDDR = G_max_VDDR*rY[15]*rY[11]*(rY[0]-E_Ca);
314
315 /* --- IKv1.1 --- */
316 double d_inf_kv11 = 1.0/(1.0+exp((rY[0]+25.0)/-7.7));
317 double f_inf_kv11 = 0.5+0.5/(1.0+exp((rY[0]+44.8)/4.4));
318 double I_kv11 = mScaleFactorCarbonMonoxide*G_max_kv11*rY[17]*rY[12]*(rY[0]-E_K);
319
320 /* --- IERG --- */
321 double d_inf_ERG = 0.2+0.8/(1.0+exp((rY[0]+20.0)/-1.8));
322 double I_ERG = mScaleFactorCarbonMonoxide*G_max_ERG*rY[7]*(rY[0]-E_K);
323
324 /* --- IBK --- */
325 //LUT d_BK = 1.0/(1.0+exp((rY[0]/-17.0)-2.0*log(rY[1]/0.001)));
326 double d_BK = 1.0/(1.0+((exp(rY[0]/-17.0))/((rY[1]/0.001)*(rY[1]/0.001))));
327 double I_BK = (G_max_BK+T_correction_BK)*d_BK*(rY[0]-E_K);
328
329 /* --- IKb --- */
330 double I_bk = mScaleFactorCarbonMonoxide*G_max_bk*(rY[0]-E_K);
331
332 /* --- ICaCL --- */
333 double tmp1 = 0.00014/rY[1];
334 double d_inf_CaCl = 1.0/(1.0+(tmp1*tmp1*tmp1));
335 double I_CaCl = G_max_CaCl*rY[6]*(rY[0]-E_Cl);
336
337 /* --- INSCC --- */
338 double d_inf_NSCC = 1.0/(1.0+pow(0.0000745/rY[3], -85.0));
339 double I_NSCC = G_max_NSCC*rY[9]*(rY[0]-E_NSCC);
340
341 /* --- JpmCa --- */
342 double J_PMCA = J_max_PMCA*1.0/(1.0+(0.000298/rY[1]));
343
344 /* ----------------- */
345 /* ER fluxes */
346 /* ----------------- */
347
348 //tmp1 = IP3/(IP3+d_IP3);
350 double tmp2 = rY[3]/(rY[3]+d_ACT);
351 double J_ERout = (Jmax_IP3*tmp1*tmp1*tmp1*tmp2*tmp2*tmp2*rY[5]*rY[5]*rY[5]+J_ERleak)*(rY[2]-rY[3]);
352 double J_SERCA = mScaleFactorSerca*Jmax_serca*rY[3]*rY[3]/(k_serca*k_serca+rY[3]*rY[3]);
353
354 /* ----------------- */
355 /* Mito fluxes */
356 /* ----------------- */
357
358 /* Uniporter */
359 tmp1 = 1.0+rY[3]/K_trans;
360 double MWC = conc*(rY[3]/K_trans)*tmp1*tmp1*tmp1/(tmp1*tmp1*tmp1*tmp1+L/pow(1.0+rY[3]/K_act, na));
361 double J_uni = Jmax_uni*(MWC-rY[4]*e2FoRTdPsiMdPsiS)*2.0*FoRT*(deltaPsi-deltaPsi_star)/(1.0-e2FoRTdPsiMdPsiS);
362
363 /* NaCa Exchanger */
364 double J_NaCa = Jmax_NaCa*ebFoRTdPsiMdPsiS/((1.0+K_Na*K_Na/(Na_i*Na_i))*(1.0+K_Ca/rY[4]));
365
366 /* ----------------- */
367 /* Cyto fluxes */
368 /* ----------------- */
369
370 double J_leak = J_max_leak*(rY[3]-rY[1]); /* P.U.->Cai */
371
372 /* ----------------- */
373 /* Entrainment */
374 /* ----------------- */
375
376 double E_Ca_PU = 0.5*RToF*log(Ca_o/rY[3]);
377 double I_VDDR_PU = G_max_VDDR*rY[11]*rY[15]*(rY[0]-E_Ca_PU);
378 //J_PMCA_PU = J_max_PMCA_PU*1.0/(1.0+exp(-(rY[3]-0.0001)/0.000015));
379 double J_PMCA_PU = J_max_PMCA_PU*1.0/(1.0+exp(-(rY[3]-0.0001)/0.000015));
380
381 double i_stim = GetStimulus(time);
382
383 /* -------------------- */
384 /* Resting Membrane, CO */
385 /* -------------------- */
386
387 //tmp1 = 2.8*spatVar[1]-0.1;
388 //I_kv11 = I_kv11*tmp1;
389 //I_ERG = I_ERG*tmp1;
390 //I_bk = I_bk*tmp1;
391 double voltage_derivative;
393 {
394 voltage_derivative = 0.0;
395 }
396 else
397 {
398 voltage_derivative = (-1.0 / 0.01) * (i_stim + I_Na+I_Ltype+I_VDDR+I_kv11+I_ERG+I_BK+I_CaCl+I_NSCC+I_bk+(J_PMCA*2.0*F*V_cyto/Asurf));
399 assert(!std::isnan(voltage_derivative));
400 }
401
402 rDY[0] = voltage_derivative;/* Vm */
403 rDY[1] = fc*((-I_Ltype-I_VDDR)*Asurf/(2.0*F*V_cyto)+J_leak-J_PMCA);
404 rDY[2] = fe*(J_SERCA-J_ERout);
405 rDY[3] = fc*((J_NaCa-J_uni)*V_MITO/V_PU+(J_ERout-J_SERCA)*V_ER/V_PU-J_leak*V_cyto/V_PU);
406 rDY[3]-= fc*(((mFractionOfVDDRInPU*I_VDDR_PU*Asurf)/(2.0*F*V_PU))+J_PMCA_PU); // *** new, 4% IVDDR ***
407 rDY[4] = fm*(J_uni-J_NaCa);
408 rDY[5] = 1.0*(d_INH-rY[5]*(rY[3]+d_INH))/tauh;
409 rDY[6] = (d_inf_CaCl-rY[6])/tau_d_CaCl;
410 rDY[7] = (d_inf_ERG-rY[7])/tau_d_ERG;
411 rDY[8] = (d_inf_Ltype-rY[8])/tau_d_Ltype;
412 rDY[9] = (d_inf_NSCC-rY[9])/tau_d_NSCC;
413 rDY[10] = (d_inf_Na-rY[10])/tau_d_Na;
414 rDY[11] = (d_inf_VDDR-rY[11])/tau_d_VDDR;
415 rDY[12] = (d_inf_kv11-rY[12])/tau_d_kv11;
416 rDY[13] = (f_inf_Ltype-rY[13])/tau_f_Ltype;
417 rDY[14] = (f_inf_Na-rY[14])/tau_f_Na;
418 rDY[15] = (f_inf_VDDR-rY[15])/tau_f_VDDR;
419 rDY[16] = (f_ca_inf_Ltype-rY[16])/tau_f_ca_Ltype;
420 rDY[17] = (f_inf_kv11-rY[17])/tau_f_kv11;
421 }
422
423template<>
425{
426
427 this->mSystemName = "ICC_model_Martincode";
428
429 this->mVariableNames.push_back("Vm");
430 this->mVariableUnits.push_back("mV");
431 this->mInitialConditions.push_back(-67.53988); // Vm (mV);
432
433 this->mVariableNames.push_back("Ca_i");
434 this->mVariableUnits.push_back("mM");
435 this->mInitialConditions.push_back(0.00001); // Ca_i (mM));
436
437 this->mVariableNames.push_back("Ca_ER");
438 this->mVariableUnits.push_back("mM");
439 this->mInitialConditions.push_back(0.00695); // Ca_ER (mM));
440
441 this->mVariableNames.push_back("Ca_PU");
442 this->mVariableUnits.push_back("mM");
443 this->mInitialConditions.push_back(0.000095); // Ca_PU (mM));
444
445 this->mVariableNames.push_back("Ca_m");
446 this->mVariableUnits.push_back("mM");
447 this->mInitialConditions.push_back(0.000138); // Ca_m (mM));
448
449 this->mVariableNames.push_back("h");
450 this->mVariableUnits.push_back("dimensionless");
451 this->mInitialConditions.push_back(0.939443); // h (dim));
452
453 this->mVariableNames.push_back("d_CaCl");
454 this->mVariableUnits.push_back("dimensionless");
455 this->mInitialConditions.push_back(0.00038); // d_CaCl (dim));
456
457 this->mVariableNames.push_back("d_ERG");
458 this->mVariableUnits.push_back("dimensionless");
459 this->mInitialConditions.push_back(0.2); // d_ERG (dim));
460
461 this->mVariableNames.push_back("d_Ltype");
462 this->mVariableUnits.push_back("dimensionless");
463 this->mInitialConditions.push_back(0.000008); // d_Ltype (dim));
464
465 this->mVariableNames.push_back("d_NSCC");
466 this->mVariableUnits.push_back("dimensionless");
467 this->mInitialConditions.push_back(0.0); // d_NSCC (dim));
468
469 this->mVariableNames.push_back("d_Na");
470 this->mVariableUnits.push_back("dimensionless");
471 this->mInitialConditions.push_back(0.013778); // d_Na (dim));
472
473 this->mVariableNames.push_back("d_VDDR");
474 this->mVariableUnits.push_back("dimensionless");
475 this->mInitialConditions.push_back(0.00099); // d_VDDR (dim));
476
477 this->mVariableNames.push_back("d_kv11");
478 this->mVariableUnits.push_back("dimensionless");
479 this->mInitialConditions.push_back(0.003992); // d_kv11 (dim));
480
481 this->mVariableNames.push_back("f_Ltype");
482 this->mVariableUnits.push_back("dimensionless");
483 this->mInitialConditions.push_back( 0.940072); // f_Ltype (dim));
484
485 this->mVariableNames.push_back("f_Na");
486 this->mVariableUnits.push_back("dimensionless");
487 this->mInitialConditions.push_back(0.182426); // f_Na (dim));
488
489 this->mVariableNames.push_back("f_VDDR");
490 this->mVariableUnits.push_back("dimensionless");
491 this->mInitialConditions.push_back(0.562177); // f_VDDR (dim));
492
493 this->mVariableNames.push_back("f_ca_Ltype");
494 this->mVariableUnits.push_back("dimensionless");
495 this->mInitialConditions.push_back(1.0); // f_ca_Ltype (dim));
496
497 this->mVariableNames.push_back("f_kv11");
498 this->mVariableUnits.push_back("dimensionless");
499 this->mInitialConditions.push_back(0.997143); // f_kv11 (dim));
500
501 this->mInitialised = true;
502}
503
504
505// Serialization for Boost >= 1.36
#define CHASTE_CLASS_EXPORT(T)
boost::shared_ptr< AbstractOdeSystemInformation > mpSystemInfo
void SetCarbonMonoxideScaleFactor(double scaleFactor)
double GetIIonic(const std::vector< double > *pStateVariables=NULL)
void SetIP3Concentration(double concentration)
void SetSercaPumpScaleFactor(double scaleFactor)
CorriasBuistICCModified(boost::shared_ptr< AbstractIvpOdeSolver > pSolver, boost::shared_ptr< AbstractStimulusFunction > pIntracellularStimulus)
void SetFractionOfVDDRInPU(double fraction)
void EvaluateYDerivatives(double time, const std::vector< double > &rY, std::vector< double > &rDY)
double GetCapacitance() const
static HeartConfig * Instance()
static boost::shared_ptr< OdeSystemInformation< ODE_SYSTEM > > Instance()