Chaste  Release::3.4
CorriasBuistSMCModified.cpp
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36 
37 #include <cmath>
38 #include <cassert>
39 #include <memory>
40 #include "Exception.hpp"
41 #include "OdeSystemInformation.hpp"
42 #include "CorriasBuistSMCModified.hpp"
43 #include "HeartConfig.hpp"
44 
45 
46  CorriasBuistSMCModified::CorriasBuistSMCModified(boost::shared_ptr<AbstractIvpOdeSolver> pSolver, boost::shared_ptr<AbstractStimulusFunction> pIntracellularStimulus)
48  pSolver,
49  14,
50  0,
51  pIntracellularStimulus)
52  {
54  mScaleFactorCarbonMonoxide = 1.0; // initialise to 1 --> no effect
55  mFakeIccStimulusPresent = true;//by default we use the fake ICC stimulus
56 
57  /* parameters */
58  Cm = 77.0*1e-6;// 77 pF --> microF
59 
61  Asurf = Asurf_in_cm_square / 0.01;//cm2 --> mm2 /*cell surface area (mm2)*/
62 
63  VolCell = 3.5e-6; /*cell volume (mm3)*/
64  hCa = 2.014e-4; /*conc for half inactivation of fCa */
65  sCa = 1.31e-05; /*slope factor for inactivation of fCa */
66 
67  /* concentrations */
68  Ki = 164.0; /*intra K conc (mM)*/
69  Nai = 10.0; /*intra Na conc (mM)*/
70  ACh = 1e-05; /*acetylcholine conc (mM)*/
71  CaiRest = 0.9e-04; /*baseline Ca conc (mM)*/
72 
73  /* maximum conductances*/
74  gLVA_max = 2.33766E-05; /*max conductance of ILVA*/ // (0.18 nS) * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
75  gCaL_max = 0.008441558; /*max conductance of ICaL*/ // (65.0 nS) * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
76  gBK_max = 0.005935065; /*max conductance of IBK)*/ // (45.7 nS) * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
77  gKb_max = 1.87013E-06; /*max conductance of IKb*/ // (0.0144 nS) * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
78  gKA_max = 0.001168831; /*max conductance of IKA*/ // (9.0 nS) * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
79  gKr_max = 0.004545455; /*max conductance of IKr*/ // (35.0 nS) * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
80  gNa_max = 0.00038961; /*max conductance of INa*/ // (3.0 nS) * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
81  gnsCC_max = 0.006493506; /*max conductance of InsCC*/ // (50.0 nS) * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
82  gcouple = 1.3*1e-6 / Asurf; /* coupling conductance bewteen fake ICC and SMC*/ // 1.3 nS * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
83 
84  JCaExt_max = 0.31705; /*max flux of CaSR (mM/ms)*/
85 
86  /* Temperature corrections */
87  Q10Ca = 2.1; /*(dim)*/
88  Q10K = 1.5; /*(dim)*/ //1.365
89  Q10Na = 2.45; /*(dim)*/
90  Texp = 297.0; /*(degK)*/
91 
92  Ca_o = 2.5; // mM
93  K_o = 7.0; // mM
94  Na_o = 137.0; // mM
95 
96  /* Nernst parameters */
97  R = 8314.4; // pJ/nmol/K
98  T = 310.0; // degK
99  F = 96484.6; // nC/nmol
100  FoRT = 0.03743; // 1/mV
101  RToF = 26.7137; // mV
102 
103  T_correct_Ca = pow(Q10Ca,(T-Texp)/10.0);/*temperature correction for Ca (dim)*/
104  T_correct_K = pow(Q10K,(T-Texp)/10.0); /*temperature correction for K (dim)*/
105  T_correct_Na = pow(Q10Na,(T-Texp)/10.0);/*temperature correction for Na (dim)*/
106  T_correct_gBK = gBK_max + 1.1*(T-Texp)*1e-6/Asurf; /*temperature correction for gBK*/ // (nS) * 1e-6 (mS/nS) / Asurf (mm2) = mS/mm2
107 
108  /* Nernst potentials */
109  EK = RToF*log(K_o/Ki); /*Nernst potential for K (mV)*/
110  ENa = RToF*log(Na_o/Nai); /*Nernst potential for Na (mV)*/
111  EnsCC = -28.0; /*Nernst potential for nsCC (mV)*/
112 
113  Init();
114 
115  }
116 
118  {
119  }
120 
122  {}
123 
125  {
126  mScaleFactorCarbonMonoxide = scaleFactor;
127  }
128 
130  {
131  mFakeIccStimulusPresent = present;
132  }
133 
135  {
137  }
138 
140  {
142  }
143 
144  double CorriasBuistSMCModified::GetIIonic(const std::vector<double>* pStateVariables)
145  {
146  if (!pStateVariables) pStateVariables = &rGetStateVariables();
147  const std::vector<double>& rY = *pStateVariables;
148 
149  double ECa = 0.5*RToF*log(Ca_o/rY[13]);
150 
151  /* inward sodium current */
152  double INa = gNa_max*rY[6]*rY[7]*(rY[0]-ENa);
153 
154  /* L-type calcium current */
155  double ICaL = gCaL_max*rY[1]*rY[2]*rY[3]*(rY[0]-ECa);
156 
157  /* low voltage activated (T-type) calcium current */
158  double ILVA = gLVA_max*rY[4]*rY[5]*(rY[0]-ECa);
159 
160  /* large conductance calcium activated potassium current */
161  double Po_BK = 1.0/(1.0+exp(-(rY[0]/17.0)-2.0*log(rY[13]/0.001)));
162  double IBK = T_correct_gBK*Po_BK*(rY[0]-EK);
163 
164  /* delayed rectifier potassium current */
165  double IKr = mScaleFactorCarbonMonoxide*gKr_max*rY[9]*rY[10]*(rY[0]-EK);
166 
167  /* A-type potassium current */
168  double IKA = mScaleFactorCarbonMonoxide*gKA_max*rY[11]*rY[12]*(rY[0]-EK);
169 
170  /* background (leakage) potassium current */
171  double IKb = mScaleFactorCarbonMonoxide*gKb_max*(rY[0]-EK);
172 
173  /* non-specific cation current */
174  double hCa_nsCC = 1.0/(1.0+pow((rY[13]/0.0002),-4.0));
175  double rACh_nsCC = 1.0/(1.0+(0.01/ACh));
176  double InsCC = gnsCC_max*rY[8]*rACh_nsCC*hCa_nsCC*(rY[0]-EnsCC);
177 
178  /* phenomenological calcium extrusion current */
179  double JCaExt = JCaExt_max*pow(rY[13],1.34);
180 
181  //i_ionic_in microA/mm2
182  double i_ionic = INa+ICaL+ILVA+IKr+IKA+IBK+IKb+InsCC+(JCaExt*2.0*F*VolCell/Asurf);
183 
184  assert(!std::isnan(i_ionic));
188  return i_ionic / 0.01;
189  }
190 
191  void CorriasBuistSMCModified::EvaluateYDerivatives(double time, const std::vector<double>& rY, std::vector<double>& rDY)
192  {
193 
194  // index [0] = -69.8; // Vm (mV)
195  // index [1] = 5.0e-6; // d_CaL (dim)
196  // index [2] = 0.953; // f_CaL (dim)
197  // index [3] = 1.0; // fCa_CaL (dim)
198  // index [4] = 0.0202; // d_LVA (dim)
199  // index [5] = 1.0; // f_LVA (dim)
200  // index [6] = 0.0086; // d_Na (dim)
201  // index [7] = 0.061; // f_Na (dim)
202  // index [8] = 0.096; // m_nsCC (dim)
203  // index [9] = 1.92e-4; // xr1 (dim)
204  // index [10] = 0.812; // xr2 (dim)
205  // index [11] = 0.00415; // xa1 (dim)
206  // index [12] = 0.716; // xa2 (dim)
207  // index [13] = 0.9e-04; // Cai (mM)
208 
209  double ECa = 0.5*RToF*log(Ca_o/rY[13]);
210 
211  /* inward sodium current */
212  double inf_d_Na = 1.0/(1.0+exp(-(rY[0]+47.0)/4.8));
213  double tau_d_Na = (0.44-0.017*rY[0])*T_correct_Na;
214  double inf_f_Na = 1.0/(1.0+exp((rY[0]+78.0)/3.0));
215  double tau_f_Na = (5.5-0.25*rY[0])*T_correct_Na;
216 
217  double INa = gNa_max*rY[6]*rY[7]*(rY[0]-ENa);
218 
219  /* L-type calcium current */
220  double inf_d_CaL = 1.0/(1.0+exp(-(rY[0]+17.0)/4.3));
221  double tau_d_CaL = 0.47*T_correct_Ca;
222 
223  double inf_f_CaL = 1.0/(1.0+exp((rY[0]+43.0)/8.9));
224  double tau_f_CaL = 86.0*T_correct_Ca;
225 
226  double inf_fCa_CaL = 1.0-(1.0/(1.0+exp(-((rY[13]-CaiRest)-hCa)/sCa)));
227  double tau_fCa_CaL = 2.0*T_correct_Ca;
228  double ICaL = gCaL_max*rY[1]*rY[2]*rY[3]*(rY[0]-ECa);
229 
230  /* low voltage activated (T-type) calcium current */
231  double inf_d_LVA = 1.0/(1.0+exp(-(rY[0]+27.5)/10.9));
232  double tau_d_LVA = 3.0*T_correct_Ca;
233 
234  double inf_f_LVA = 1.0/(1.0+exp((rY[0]+15.8)/7.0));
235  double tau_f_LVA = 7.58*exp(rY[0]*0.00817)*T_correct_Ca;
236 
237  double ILVA = gLVA_max*rY[4]*rY[5]*(rY[0]-ECa);
238 
239  /* large conductance calcium activated potassium current */
240  double Po_BK = 1.0/(1.0+exp(-(rY[0]/17.0)-2.0*log(rY[13]/0.001)));
241  double IBK = T_correct_gBK*Po_BK*(rY[0]-EK);
242 
243  /* delayed rectifier potassium current */
244  double inf_xr1 = 1.0/(1.0+exp(-(rY[0]+27.0)/5.0));
245  double tau_xr1 = 80.0*T_correct_K;
246 
247  double inf_xr2 = 0.2+0.8/(1.0+exp((rY[0]+58.0)/10.0));
248  double tau_xr2 = (-707.0+1481.0*exp((rY[0]+36.0)/95.0))*T_correct_K;
249 
250  double IKr = mScaleFactorCarbonMonoxide*gKr_max*rY[9]*rY[10]*(rY[0]-EK);
251 
252  /* A-type potassium current */
253  double inf_xa1 = 1.0/(1.0+exp(-(rY[0]+26.5)/7.9));
254  double tau_xa1 = (31.8+175.0*exp(-0.5*pow(((rY[0]+44.4)/22.3),2.0)))*T_correct_K;
255 
256  double inf_xa2 = 0.1+0.9/(1.0+exp((rY[0]+65.0)/6.2));
257  double tau_xa2 = 90.0*T_correct_K;
258 
259  double IKA = mScaleFactorCarbonMonoxide*gKA_max*rY[11]*rY[12]*(rY[0]-EK);
260 
261  /* background (leakage) potassium current */
262  double IKb = mScaleFactorCarbonMonoxide*gKb_max*(rY[0]-EK);
263 
264  /* non-specific cation current */
265  double inf_m_nsCC = 1.0/(1.0+exp(-(rY[0]+25.0)/20.0));
266  double tau_m_nsCC = 150.0/(1.0+exp(-(rY[0]+66.0)/26.0));
267  double hCa_nsCC = 1.0/(1.0+pow((rY[13]/0.0002),-4.0));
268  double rACh_nsCC = 1.0/(1.0+(0.01/ACh));
269 
270  double InsCC = gnsCC_max*rY[8]*rACh_nsCC*hCa_nsCC*(rY[0]-EnsCC);
271 
272  /* phenomenological calcium extrusion current */
273  double JCaExt = JCaExt_max*pow(rY[13],1.34);
274 
275 
276  double t_ICCplateau = 7582.0; // time_units
277  double V_decay = 37.25; // voltage_units
278  double t_ICCpeak = 98.0; // time_units
279 
280  double period = 20000.0; // time_units
281  double stim_start = ((time > (period * 1.0)) && (time <= (period * 2.0))) ? (period * 1.0) : ((time > (period * 2.0)) && (time <= (period * 3.0))) ? (period * 2.0) : ((time > (period * 3.0)) && (time <= (period * 4.0))) ? (period * 3.0) : ((time > (period * 4.0)) && (time <= (period * 5.0))) ? (period * 4.0) : 0.0; // time_units
282  double local_time = time - (stim_start + t_ICCpeak); // time_units
283  double t_ICC_stimulus = 10000.0; // time_units
284  double delta_VICC = 59.0; // voltage_units
285 
286  double i_stim;
287  //see whether we are running this in isolaation (and we need the fake ICC stimulus) or coupled to a real ICC model
289  {
290  //for single cell simulations where we want the fake ICC stimulus in
291  i_stim = (local_time < t_ICCpeak) ? (gcouple * delta_VICC) : ((local_time >= t_ICCpeak) && (local_time <= t_ICCplateau)) ? (gcouple * delta_VICC * (1.0 / (1.0 + exp((local_time - 8000.0) / 1000.0)))) : ((local_time > t_ICCplateau) && (local_time < t_ICC_stimulus)) ? (gcouple * V_decay * (1.0 / (1.0 + exp((local_time - 8000.0) / 150.0)))) : 0.0; // current_units
292  }
293  else
294  {
295  i_stim = GetStimulus(time);//for tissue simulations with current injected into SMC
296  }
297 
298  /* membrane potential */
299  double Iion = INa+ICaL+ILVA+IKr+IKA+IBK+IKb+InsCC+(JCaExt*2.0*F*VolCell/Asurf);
300 
301  double voltage_derivative;
303  {
304  voltage_derivative = 0.0;
305  }
306  else
307  {
308  voltage_derivative = (-1.0 / 0.01) * (-i_stim + Iion);//microA/mm2---> microA/cm2
309  //std::cout<<rY[0]<<std::endl;
310  assert(!std::isnan(voltage_derivative));
311  }
312 
313  rDY[0] = voltage_derivative;/* Vm */
314  rDY[1] = (inf_d_CaL - rY[1])/tau_d_CaL;
315  rDY[2] = (inf_f_CaL - rY[2])/tau_f_CaL;
316  rDY[3] = (inf_fCa_CaL - rY[3])/tau_fCa_CaL;
317  rDY[4] = (inf_d_LVA - rY[4])/tau_d_LVA;
318  rDY[5] = (inf_f_LVA - rY[5])/tau_f_LVA;
319  rDY[6] = (inf_d_Na - rY[6])/tau_d_Na;
320  rDY[7] = (inf_f_Na - rY[7])/tau_f_Na;
321  rDY[8] = (inf_m_nsCC - rY[8])/tau_m_nsCC;
322  rDY[9] = (inf_xr1 - rY[9])/tau_xr1;
323  rDY[10] = (inf_xr2 - rY[10])/tau_xr2;
324  rDY[11] = (inf_xa1 - rY[11])/tau_xa1;
325  rDY[12] = (inf_xa2 - rY[12])/tau_xa2;
326  rDY[13] = (-(ICaL+ILVA)*Asurf/(2.0*F*VolCell)-JCaExt); /* intracellular calcium *1000 M-> mM; /1000 F units*/
327  }
328 
329 template<>
331 {
332  // Time units: time_units
333  //
334  this->mSystemName = "SMC_model_Martincode";
335 
336  this->mVariableNames.push_back("Vm_SM");
337  this->mVariableUnits.push_back("mV");
338  this->mInitialConditions.push_back(-69.8); // Vm (mV)
339 
340  this->mVariableNames.push_back("d_CaL");
341  this->mVariableUnits.push_back("dim");
342  this->mInitialConditions.push_back(5.0e-6); // d_CaL (dim));
343 
344  this->mVariableNames.push_back("f_CaL");
345  this->mVariableUnits.push_back("dim");
346  this->mInitialConditions.push_back(0.953); // f_CaL (dim)
347 
348  this->mVariableNames.push_back("fCa_CaL");
349  this->mVariableUnits.push_back("dim");
350  this->mInitialConditions.push_back(1.0); // fCa_CaL (dim)
351 
352  this->mVariableNames.push_back("d_LVA");
353  this->mVariableUnits.push_back("dim");
354  this->mInitialConditions.push_back(0.0202); // d_LVA (dim)
355 
356  this->mVariableNames.push_back("f_LVA");
357  this->mVariableUnits.push_back("dim");
358  this->mInitialConditions.push_back(1.0); // f_LVA (dim)
359 
360  this->mVariableNames.push_back("d_Na");
361  this->mVariableUnits.push_back("dim");
362  this->mInitialConditions.push_back(0.0086); // d_Na (dim)
363 
364  this->mVariableNames.push_back("f_Na");
365  this->mVariableUnits.push_back("dim");
366  this->mInitialConditions.push_back(0.061); // f_Na (dim)
367 
368  this->mVariableNames.push_back("m_nsCC");
369  this->mVariableUnits.push_back("dim");
370  this->mInitialConditions.push_back(0.096); // m_nsCC (dim)
371 
372  this->mVariableNames.push_back("xr1");
373  this->mVariableUnits.push_back("dim");
374  this->mInitialConditions.push_back(1.92e-4); // xr1 (dim)
375 
376  this->mVariableNames.push_back("xr2");
377  this->mVariableUnits.push_back("dim");
378  this->mInitialConditions.push_back(0.812); // xr2 (dim)
379 
380  this->mVariableNames.push_back("xa1");
381  this->mVariableUnits.push_back("dim");
382  this->mInitialConditions.push_back(0.00415); // xa1 (dim)
383 
384  this->mVariableNames.push_back("xa2");
385  this->mVariableUnits.push_back("dim");
386  this->mInitialConditions.push_back(0.716); // xa2 (dim)
387 
388  this->mVariableNames.push_back("Cai");
389  this->mVariableUnits.push_back("mM");
390  this->mInitialConditions.push_back(0.9e-04); // Cai (mM)
391 
392  this->mInitialised = true;
393 }
394 
395 
396 // Serialization for Boost >= 1.36
static boost::shared_ptr< OdeSystemInformation< ODE_SYSTEM > > Instance()
double SetCarbonMonoxideScaleFactor()
CorriasBuistSMCModified(boost::shared_ptr< AbstractIvpOdeSolver > pSolver, boost::shared_ptr< AbstractStimulusFunction > pIntracellularStimulus)
void EvaluateYDerivatives(double time, const std::vector< double > &rY, std::vector< double > &rDY)
void SetFakeIccStimulusPresent(bool present)
double GetIIonic(const std::vector< double > *pStateVariables=NULL)
boost::shared_ptr< AbstractOdeSystemInformation > mpSystemInfo
double GetCapacitance() const
#define CHASTE_CLASS_EXPORT(T)
static HeartConfig * Instance()