/* * Quantitative cellular description of gastric slow wave activity * * Model Status * * This model is known to run in JSIM, COR and OpenCell to recreate * the published results. The units have been checked and they * are consistent. The CellML model was created by Alberto Corrias * and taken from the NUS Computational Bioengineering Laboratory * website. * * Model Structure * * Abstract: Interstitial cells of Cajal (ICC) are responsible * for the spontaneous and omnipresent electrical activity in the * stomach. A quantitative description of the intracellular processes * whose coordinated activity is believed to generate electrical * slow waves has been developed and is presented here. In line * with recent experimental evidence, the model describes how the * interplay between the mitochondria and the endoplasmic reticulum * in cycling intracellular Ca2+ provides the primary regulatory * signal for the initiation of the slow wave. The major ion channels * that have been identified as influencing slow wave activity * have been modeled according to data obtained from isolated ICC. * The model has been validated by comparing the simulated profile * of the slow waves with experimental recordings and shows good * correspondence in terms of frequency, amplitude, and shape in * both control and pharmacologically altered conditions. * * The complete original paper reference is cited below: * * Quantitative cellular description of gastric slow wave activity, * Alberto Corrias, Martin L. Buist 2008, Am J Physiol Gastrointest * Liver Physiol , 294, G989-G995. PubMed ID: 18276830 * * The documented original is available at the National University * of Singapore's Computational Bioengineering Laboratory website. * * Corrias 2008 diagram * * [[Image file: corrias_2008.png]] * * Schematic view of the model. The intracellular space is divided * in four compartments: cytoplasm, mitochondria, endoplasmic reticulum * (ER), and submembrane space (SS). All membrane ion channels * and transport mechanisms included in the model are depicted. */ import nsrunit; unit conversion on; unit conductance_units=1E-9 kilogram^(-1)*meter^(-2)*second^3*ampere^2; unit millifarads=.001 kilogram^(-1)*meter^(-2)*second^4*ampere^2; unit voltage_units=.001 kilogram^1*meter^2*second^(-3)*ampere^(-1); unit volume_units=.001 meter^3; unit Inverse_Voltage_units=1E3 kilogram^(-1)*meter^(-2)*second^3*ampere^1; unit time_units=1 second^1; unit current_units=1E-12 ampere^1; unit rate_constants_units=1 second^(-1); unit capacitance_units=1E-9 kilogram^(-1)*meter^(-2)*second^4*ampere^2; unit Temperature_units=1 kelvin^1; unit Inverse_Temperature_units_times_conductance=1E-9 kilogram^(-1)*meter^(-2)*second^3*ampere^2*kelvin^(-1); unit F_units=1E3 second^1*ampere^1*mole^(-1); unit R_units=1 kilogram^1*meter^2*second^(-2)*kelvin^(-1)*mole^(-1); // unit millimolar predefined unit per_millimolar=1 meter^3*mole^(-1); unit millimolar_per_second=1 meter^(-3)*second^(-1)*mole^1; unit millimolar_per_second_per_millivolt=1E3 kilogram^(-1)*meter^(-5)*second^2*ampere^1*mole^1; unit millimole_to_nanomole=1E-6 dimensionless; unit microcoulomb_to_picocoulomb=1E-6 dimensionless; unit Inverse_Voltage_Units_per_time_units=1E3 kilogram^(-1)*meter^(-2)*second^2*ampere^1; math main { realDomain time time_units; time.min=0; extern time.max; extern time.delta; real T Temperature_units; T=310; real T_exp Temperature_units; T_exp=297; real F F_units; F=96.4846; real R R_units; R=8.3144; real Q10Ca dimensionless; Q10Ca=2.1; real Q10K dimensionless; Q10K=1.5; real Q10Na dimensionless; Q10Na=2.45; real Ca_o millimolar; Ca_o=2.5; real Na_o millimolar; Na_o=137; real K_o millimolar; K_o=7; real Cl_o millimolar; Cl_o=134; real T_correction_Na dimensionless; real T_correction_K dimensionless; real T_correction_Ca dimensionless; real T_correction_BK conductance_units; real FoRT Inverse_Voltage_units; real RToF voltage_units; real Cm capacitance_units; Cm=0.025; real Vol volume_units; Vol=1e-12; real P_cyto dimensionless; P_cyto=0.7; real V_cyto volume_units; real fc dimensionless; fc=0.01; real Vm(time) voltage_units; when(time=time.min) Vm=-67; real Ca_i(time) millimolar; when(time=time.min) Ca_i=0.00000993087; real Na_i millimolar; Na_i=30; real K_i millimolar; K_i=120; real Cl_i millimolar; Cl_i=88; real J_leak(time) millimolar_per_second; real I_Na(time) current_units; real I_Ltype(time) current_units; real I_VDDR(time) current_units; real I_kv11(time) current_units; real I_BK(time) current_units; real I_ERG(time) current_units; real I_CaCl(time) current_units; real I_NSCC(time) current_units; real I_bk(time) current_units; real J_PMCA(time) millimolar_per_second; real d_inf_Ltype(time) dimensionless; real tau_d_Ltype time_units; real d_Ltype(time) dimensionless; when(time=time.min) d_Ltype=0; real f_inf_Ltype(time) dimensionless; real tau_f_Ltype time_units; real f_Ltype(time) dimensionless; when(time=time.min) f_Ltype=1; real f_ca_inf_Ltype(time) dimensionless; real tau_f_ca_Ltype time_units; real f_ca_Ltype(time) dimensionless; when(time=time.min) f_ca_Ltype=1; real I_Ltype.E_Ca(time) voltage_units; real G_max_Ltype conductance_units; G_max_Ltype=2; real J_max_PMCA millimolar_per_second; J_max_PMCA=0.088464; real d_inf_VDDR(time) dimensionless; real tau_d_VDDR time_units; real d_VDDR(time) dimensionless; when(time=time.min) d_VDDR=0; real f_inf_VDDR(time) dimensionless; real tau_f_VDDR time_units; real f_VDDR(time) dimensionless; when(time=time.min) f_VDDR=1; real I_VDDR.E_Ca(time) voltage_units; real G_max_VDDR conductance_units; G_max_VDDR=3; real d_inf_CaCl(time) dimensionless; real tau_d_CaCl time_units; tau_d_CaCl=0.03; real d_CaCl(time) dimensionless; when(time=time.min) d_CaCl=0; real E_Cl voltage_units; real G_max_CaCl conductance_units; G_max_CaCl=10.1; real d_BK(time) dimensionless; real I_BK.E_K voltage_units; real G_max_BK conductance_units; G_max_BK=23; real I_bk.E_K voltage_units; real G_max_bk conductance_units; G_max_bk=0.15; real d_inf_ERG(time) dimensionless; real tau_d_ERG time_units; real d_ERG(time) dimensionless; when(time=time.min) d_ERG=0; real I_ERG.E_K voltage_units; real G_max_ERG conductance_units; G_max_ERG=2.5; real d_inf_kv11(time) dimensionless; real tau_d_kv11 time_units; real d_kv11(time) dimensionless; when(time=time.min) d_kv11=0; real f_inf_kv11(time) dimensionless; real tau_f_kv11 time_units; real f_kv11(time) dimensionless; when(time=time.min) f_kv11=1; real I_kv11.E_K voltage_units; real G_max_kv11 conductance_units; G_max_kv11=6.3; real d_inf_Na(time) dimensionless; real tau_d_Na time_units; real d_Na(time) dimensionless; when(time=time.min) d_Na=0; real f_inf_Na(time) dimensionless; real tau_f_Na time_units; real f_Na(time) dimensionless; when(time=time.min) f_Na=1; real E_Na voltage_units; real G_max_Na conductance_units; G_max_Na=20; real Ca_PU(time) millimolar; when(time=time.min) Ca_PU=0.0000902; real d_inf_NSCC(time) dimensionless; real tau_d_NSCC time_units; tau_d_NSCC=0.35; real d_NSCC(time) dimensionless; when(time=time.min) d_NSCC=0; real E_NSCC voltage_units; real G_max_NSCC conductance_units; G_max_NSCC=12.15; real NaPerm_o_Kperm dimensionless; NaPerm_o_Kperm=1.056075; real P_PU dimensionless; P_PU=0.001; real P_mito dimensionless; P_mito=0.12871; real P_ER dimensionless; P_ER=0.1; real V_MITO volume_units; real V_ER volume_units; real V_PU volume_units; real fe dimensionless; fe=0.01; real fm dimensionless; fm=0.0003; real Ca_m(time) millimolar; when(time=time.min) Ca_m=0.000136; real Ca_ER(time) millimolar; when(time=time.min) Ca_ER=0.007299; real ADP_m(time) millimolar; when(time=time.min) ADP_m=2.60093454; real ADP_i(time) millimolar; when(time=time.min) ADP_i=0.0077282; real NADH_m(time) millimolar; when(time=time.min) NADH_m=0.101476; real h(time) dimensionless; when(time=time.min) h=0.9397; real IP3 millimolar; IP3=0.0006; real deltaPsi(time) voltage_units; when(time=time.min) deltaPsi=164.000044; real deltapH dimensionless; deltapH=-0.4; real Cmito millifarads; Cmito=0.006995; real K_res dimensionless; K_res=1.35e18; real r1 dimensionless; r1=2.077e-18; real r2 dimensionless; r2=1.728e-9; real r3 dimensionless; r3=1.059e-26; real ra rate_constants_units; ra=6.394e-10; real rb rate_constants_units; rb=1.762e-13; real rc1 rate_constants_units; rc1=2.656e-19; real rc2 rate_constants_units; rc2=8.632e-27; real deltaPsi_B voltage_units; deltaPsi_B=50; real g dimensionless; g=0.85; real K_F1 millimolar; K_F1=1.71e9; real Pi_m millimolar; Pi_m=20; real p1 dimensionless; p1=1.346e-8; real p2 dimensionless; p2=7.739e-7; real p3 dimensionless; p3=6.65e-15; real pa rate_constants_units; pa=1.656e-5; real pb rate_constants_units; pb=3.373e-7; real pc1 rate_constants_units; pc1=9.651e-14; real pc2 rate_constants_units; pc2=4.845e-19; real frac dimensionless; frac=0.5; real K_act millimolar; K_act=0.00038; real na dimensionless; na=2.8; real deltaPsi_star voltage_units; deltaPsi_star=91; real K_Na millimolar; K_Na=9.4; real K_Ca millimolar; K_Ca=0.003; real K_trans millimolar; K_trans=0.006; real L dimensionless; L=50; real b dimensionless; b=0.5; real beta_max rate_constants_units; beta_max=2.055; real beta1 per_millimolar; beta1=1.66; real beta2 per_millimolar; beta2=0.0249; real beta3 per_millimolar; beta3=4; real beta4 per_millimolar; beta4=2.83; real beta5 per_millimolar; beta5=1.3; real beta6 per_millimolar; beta6=2.66; real beta7 per_millimolar; beta7=0.16; real KCa_PDH millimolar; KCa_PDH=0.00005; real u1 dimensionless; u1=15; real u2 dimensionless; u2=1.1; real n dimensionless; n=2; real K_Glc millimolar; K_Glc=8.7; real nhyd dimensionless; nhyd=2.7; real K_hyd rate_constants_units; K_hyd=0.05125; real J_ERleak rate_constants_units; J_ERleak=1.666667; real Jmax_IP3 rate_constants_units; Jmax_IP3=50000; real d_IP3 millimolar; d_IP3=0.00025; real d_ACT millimolar; d_ACT=0.001; real d_INH millimolar; d_INH=0.0014; real tauh time_units; tauh=4; real Jmax_serca millimolar_per_second; Jmax_serca=1.8333; real k_serca millimolar; k_serca=0.00042; real conc millimolar; conc=0.001; real Jmax_uni rate_constants_units; Jmax_uni=5000; real Jmax_NaCa millimolar_per_second; Jmax_NaCa=0.05; real J_max_leak rate_constants_units; J_max_leak=0.01; real rho_res millimolar; rho_res=0.4; real rho_F1 millimolar; rho_F1=0.7; real g_H millimolar_per_second_per_millivolt; g_H=0.0033333; real J_red_basal millimolar_per_second; J_red_basal=0.3333; real Jmax_ANT millimolar_per_second; Jmax_ANT=15; real J_hyd_max millimolar_per_second; J_hyd_max=0.037625; real Glc millimolar; Glc=1; real total_NAD_m millimolar; total_NAD_m=8; real total_ANP_m millimolar; total_ANP_m=12; real total_ANP_i millimolar; total_ANP_i=2; real NAD_m(time) millimolar; real ATP_m(time) millimolar; real ADP_mfree(time) millimolar; real ADP3_m(time) millimolar; real ATP4_m(time) millimolar; real ATP_i(time) millimolar; real ADP_ifree(time) millimolar; real ADP3_i(time) millimolar; real MgADP_i(time) millimolar; real ATP4_i(time) millimolar; real J_ERout(time) millimolar_per_second; real J_SERCA(time) millimolar_per_second; real MWC(time) millimolar; real J_uni(time) millimolar_per_second; real J_NaCa(time) millimolar_per_second; real J_red(time) millimolar_per_second; real J_pTCA(time) millimolar_per_second; real A_F1(time) voltage_units; real J_pF1(time) millimolar_per_second; real J_HF1(time) millimolar_per_second; real A_res(time) voltage_units; real J_o(time) millimolar_per_second; real J_glyTotal(time) millimolar_per_second; real f_PDHa(time) dimensionless; real J_Hres(time) millimolar_per_second; real J_ANT(time) millimolar_per_second; real PMF(time) voltage_units; real J_Hleak(time) millimolar_per_second; real J_pGly(time) millimolar_per_second; real J_hydSS millimolar_per_second; real J_hyd(time) millimolar_per_second; // // FoRT=(F/(R*T)); RToF=(R*T/F); T_correction_Ca=(Q10Ca^((T-T_exp)/(10 Temperature_units))); T_correction_K=(Q10K^((T-T_exp)/(10 Temperature_units))); T_correction_Na=(Q10Na^((T-T_exp)/(10 Temperature_units))); T_correction_BK=((1.1 Inverse_Temperature_units_times_conductance)*(T-T_exp)); // V_cyto=(Vol*P_cyto); Vm:time=((-1)*1*1/Cm*(I_Na+I_Ltype+I_VDDR+I_kv11+I_ERG+I_BK+I_CaCl+I_NSCC+I_bk+J_PMCA*2*(1E6 millimole_to_nanomole)*(1E6 microcoulomb_to_picocoulomb)*F*V_cyto)); Ca_i:time=(fc*(((-1)*1*I_Ltype+(-1)*1*I_VDDR)/(2*(1E6 millimole_to_nanomole)*(1E6 microcoulomb_to_picocoulomb)*F*V_cyto)+J_leak+(-1)*1*J_PMCA)); // d_inf_Ltype=(1/(1+exp((Vm+(17 voltage_units))/((-1)*(4.3 voltage_units))))); tau_d_Ltype=(T_correction_Ca*(.001 time_units)); d_Ltype:time=((d_inf_Ltype-d_Ltype)/tau_d_Ltype); // f_inf_Ltype=(1/(1+exp((Vm+(43 voltage_units))/(8.9 voltage_units)))); tau_f_Ltype=(T_correction_Ca*(.086 time_units)); f_Ltype:time=((f_inf_Ltype-f_Ltype)/tau_f_Ltype); // f_ca_inf_Ltype=(1-1/(1+exp((Ca_i-(1E-4 millimolar)-(2.14E-4 millimolar))/((-1)*(1.31E-5 millimolar))))); tau_f_ca_Ltype=(T_correction_Ca*(.002 time_units)); f_ca_Ltype:time=((f_ca_inf_Ltype-f_ca_Ltype)/tau_f_ca_Ltype); // I_Ltype.E_Ca=(.5*RToF*ln(Ca_o/Ca_i)); I_Ltype=(G_max_Ltype*f_Ltype*d_Ltype*f_ca_Ltype*(Vm-I_Ltype.E_Ca)); // J_PMCA=(J_max_PMCA*1/(1+(2.98E-4 millimolar)/Ca_i)); // d_inf_VDDR=(1/(1+exp((Vm+(26 voltage_units))/((-1)*(6 voltage_units))))); tau_d_VDDR=(T_correction_Ca*(.006 time_units)); d_VDDR:time=((d_inf_VDDR-d_VDDR)/tau_d_VDDR); // f_inf_VDDR=(1/(1+exp((Vm+(66 voltage_units))/(6 voltage_units)))); tau_f_VDDR=(T_correction_Ca*(.04 time_units)); f_VDDR:time=((f_inf_VDDR-f_VDDR)/tau_f_VDDR); // I_VDDR.E_Ca=(.5*RToF*ln(Ca_o/Ca_i)); I_VDDR=(G_max_VDDR*f_VDDR*d_VDDR*(Vm-I_VDDR.E_Ca)); // d_inf_CaCl=(1/(1+((1.4E-4 millimolar)/Ca_i)^3)); d_CaCl:time=((d_inf_CaCl-d_CaCl)/tau_d_CaCl); // E_Cl=(RToF*ln(Cl_i/Cl_o)); I_CaCl=(G_max_CaCl*d_CaCl*(Vm-E_Cl)); // d_BK=(1/(1+exp(Vm/((-1)*(17 voltage_units))-2*ln(Ca_i/(.001 millimolar))))); // I_BK.E_K=(RToF*ln(K_o/K_i)); I_BK=((G_max_BK+T_correction_BK)*d_BK*(Vm-I_BK.E_K)); // I_bk.E_K=(RToF*ln(K_o/K_i)); I_bk=(G_max_bk*(Vm-I_bk.E_K)); // d_inf_ERG=(.2+.8/(1+exp((Vm+(20 voltage_units))/((-1)*(1.8 voltage_units))))); tau_d_ERG=(T_correction_K*(.003 time_units)); d_ERG:time=((d_inf_ERG-d_ERG)/tau_d_ERG); // I_ERG.E_K=(RToF*ln(K_o/K_i)); I_ERG=(G_max_ERG*d_ERG*(Vm-I_ERG.E_K)); // d_inf_kv11=(1/(1+exp((Vm+(25 voltage_units))/((-1)*(7.7 voltage_units))))); tau_d_kv11=(T_correction_K*(.005 time_units)); d_kv11:time=((d_inf_kv11-d_kv11)/tau_d_kv11); // f_inf_kv11=(.5+.5/(1+exp((Vm+(44.8 voltage_units))/(4.4 voltage_units)))); tau_f_kv11=(T_correction_K*(.005 time_units)); f_kv11:time=((f_inf_kv11-f_kv11)/tau_f_kv11); // I_kv11.E_K=(RToF*ln(K_o/K_i)); I_kv11=(G_max_kv11*f_kv11*d_kv11*(Vm-I_kv11.E_K)); // d_inf_Na=(1/(1+exp((Vm+(47 voltage_units))/((-1)*(4.8 voltage_units))))); tau_d_Na=(T_correction_Na*(.003 time_units)); d_Na:time=((d_inf_Na-d_Na)/tau_d_Na); // f_inf_Na=(1/(1+exp((Vm+(78 voltage_units))/(7 voltage_units)))); tau_f_Na=(T_correction_Na*(.0016 time_units)); f_Na:time=((f_inf_Na-f_Na)/tau_f_Na); // E_Na=(RToF*ln(Na_o/Na_i)); I_Na=(G_max_Na*f_Na*d_Na*(Vm-E_Na)); // d_inf_NSCC=(1/(1+((7.45E-5 millimolar)/Ca_PU)^((-1)*85))); d_NSCC:time=((d_inf_NSCC-d_NSCC)/tau_d_NSCC); // E_NSCC=(RToF*ln((K_o+Na_o*NaPerm_o_Kperm)/(K_i+Na_i*NaPerm_o_Kperm))); I_NSCC=(G_max_NSCC*d_NSCC*(Vm-E_NSCC)); // V_MITO=(Vol*P_mito); V_PU=(Vol*P_PU); V_ER=(Vol*P_ER); J_ERout=((Jmax_IP3*(IP3/(IP3+d_IP3))^3*(Ca_PU/(Ca_PU+d_ACT))^3*h^3+J_ERleak)*(Ca_ER-Ca_PU)); J_SERCA=(Jmax_serca*Ca_PU^2/(k_serca^2+Ca_PU^2)); MWC=(conc*Ca_PU/K_trans*(1+Ca_PU/K_trans)^3/((1+Ca_PU/K_trans)^4+L/(1+Ca_PU/K_act)^na)); J_uni=(Jmax_uni*(MWC-Ca_m*exp((-1)*2*FoRT*(deltaPsi-deltaPsi_star)))*2*FoRT*(deltaPsi-deltaPsi_star)/(1-exp((-1)*2*FoRT*(deltaPsi-deltaPsi_star)))); J_NaCa=(Jmax_NaCa*exp(b*FoRT*(deltaPsi-deltaPsi_star))/((1+(K_Na/Na_i)^n)*(1+K_Ca/Ca_m))); J_leak=(J_max_leak*(Ca_PU-Ca_i)); A_res=(RToF*ln(K_res*sqrt(NADH_m)/sqrt(NAD_m))); J_o=(rho_res*.5*((ra*10^(6*deltapH)+rc1*exp(6*deltaPsi_B*FoRT))*exp(A_res*FoRT)+(-1)*1*ra*exp(g*6*FoRT*deltaPsi)+rc2*exp(FoRT*A_res)*exp(FoRT*deltaPsi*6*g))/((1+r1*exp(FoRT*A_res))*exp(FoRT*deltaPsi_B*6)+(r2+r3*exp(FoRT*A_res))*exp(FoRT*deltaPsi*g*6))); J_Hres=(rho_res*3.966*(ra*10^(6*deltapH)*exp(FoRT*A_res)+rb*10^(6*deltapH)+(-1)*1*(ra+rb)*exp(g*FoRT*deltaPsi*6))/((1+r1*exp(FoRT*A_res))*exp(6*FoRT*deltaPsi_B)+(r2+r3*exp(FoRT*A_res))*exp(g*6*FoRT*deltaPsi))); J_glyTotal=(beta_max*(1+beta1*Glc)*beta2*Glc*ATP_i/(1+beta3*ATP_i+(1+beta4*ATP_i)*beta5*Glc+(1+beta6*ATP_i)*beta7*Glc)); f_PDHa=(1/(1+u2*(1+u1/(1+Ca_m/KCa_PDH)^2))); J_red=(J_red_basal+6.3944*f_PDHa*J_glyTotal); J_pTCA=(J_red_basal/3+.84*f_PDHa*J_glyTotal); A_F1=(RToF*ln(K_F1*ATP_m/(ADP_mfree*Pi_m))); J_pF1=(rho_F1*((-1)*1)*((pa*10^(3*deltapH)+pc1*exp(3*FoRT*deltaPsi_B))*exp(FoRT*A_F1)+(-1)*1*pa*exp(3*FoRT*deltaPsi)+pc2*exp(FoRT*A_F1)*exp(3*FoRT*deltaPsi))/((1+p1*exp(FoRT*A_F1))*exp(3*FoRT*deltaPsi_B)+(p2+p3*exp(FoRT*A_F1))*exp(3*FoRT*deltaPsi))); J_HF1=((-1)*1*rho_F1*3*(pa*10^(3*deltapH)*exp(FoRT*A_F1)+pb*10^(3*deltapH)+(-1)*1*(pa+pb)*exp(3*FoRT*deltaPsi))/((1+p1*exp(FoRT*A_F1))*exp(3*FoRT*deltaPsi_B)+(p2+p3*exp(FoRT*A_F1))*exp(3*FoRT*deltaPsi))); J_ANT=(Jmax_ANT*(1-ATP4_i*ADP3_m/(ADP3_i*ATP4_m)*exp((-1)*1*FoRT*deltaPsi))/((1+ATP4_i/ADP3_i*exp((-1)*1*frac*FoRT*deltaPsi))*(1+ADP3_m/ATP4_m))); PMF=(deltaPsi-2.303*RToF*deltapH); J_Hleak=(g_H*PMF); J_pGly=(.15*J_glyTotal); J_hydSS=(J_hyd_max/(1+(K_Glc/Glc)^nhyd)); J_hyd=(K_hyd*ATP_i+J_hydSS); NADH_m:time=(J_red-J_o); NAD_m=(total_NAD_m-NADH_m); ADP_m:time=(J_ANT+(-1)*1*J_pTCA+(-1)*1*J_pF1); ATP_m=(total_ANP_m-ADP_m); ADP_mfree=(.8*ADP_m); ADP3_m=(.45*ADP_mfree); ATP4_m=(.05*ATP_m); ADP_i:time=((-1)*1*J_ANT*V_MITO/V_cyto+J_hyd+(-1)*1*J_pGly); ATP_i=(total_ANP_i-ADP_i); ADP_ifree=(.3*ADP_i); ADP3_i=(.45*ADP_ifree); MgADP_i=(.55*ADP_ifree); ATP4_i=(.05*ATP_i); Ca_PU:time=(fc*((J_NaCa-J_uni)*V_MITO/V_PU+(J_ERout-J_SERCA)*V_ER/V_PU+(-1)*1*J_leak*V_cyto/V_PU)); Ca_m:time=(fm*(J_uni-J_NaCa)); Ca_ER:time=(fe*(J_SERCA-J_ERout)); deltaPsi:time=((-1)*1*F*V_MITO*(1E6 millimole_to_nanomole)*1/Cmito*(J_Hleak+(-1)*1*J_Hres+J_ANT+J_HF1+2*J_uni)); h:time=((1 per_millimolar)*(d_INH-h*(Ca_PU+d_INH))/tauh); }