//Created by libAntimony v2.4 model grandi_pasqualini_bers_2010__environment(time_) // Variable initializations: time_ = ; end model grandi_pasqualini_bers_2010__parameters(epi, R, Frdy, Temp, FoRT, Cmem, Qpow, cellLength, cellRadius, junctionLength, junctionRadius, distSLcyto, distJuncSL, DcaJuncSL, DcaSLcyto, DnaJuncSL, DnaSLcyto, Vcell, Vmyo, Vsr, Vsl, Vjunc, SAjunc, SAsl, J_ca_juncsl, J_ca_slmyo, J_na_juncsl, J_na_slmyo, Fjunc, Fsl, Fjunc_CaL, Fsl_CaL, Cli, Clo, Ko, Nao, Cao, Mgi, ena_junc, ena_sl, ek, eca_junc, eca_sl, ecl, GNa, GNaB, IbarNaK, KmNaip, KmKo, Q10NaK, Q10KmNai, pNaK, gkp, GClCa, GClB, KdClCa, pNa, pCa, pK, Q10CaL, IbarNCX, KmCai, KmCao, KmNai, KmNao, ksat, nu, Kdact, Q10NCX, IbarSLCaP, KmPCa, GCaB, Q10SLCaP, Q10SRCaP, Vmax_SRCaP, Kmf, Kmr, hillSRCaP, ks, koCa, kom, kiCa, kim, ec50SR, Bmax_Naj, Bmax_Nasl, koff_na, kon_na, Bmax_TnClow, koff_tncl, kon_tncl, Bmax_TnChigh, koff_tnchca, kon_tnchca, koff_tnchmg, kon_tnchmg, Bmax_CaM, koff_cam, kon_cam, Bmax_myosin, koff_myoca, kon_myoca, koff_myomg, kon_myomg, Bmax_SR, koff_sr, kon_sr, Bmax_SLlowsl, Bmax_SLlowj, koff_sll, kon_sll, Bmax_SLhighsl, Bmax_SLhighj, koff_slh, kon_slh, Bmax_Csqn, koff_csqn, kon_csqn, Na_j, Na_sl, K_i, Ca_j, Ca_sl) // Assignment Rules: epi := 1; R := 8314; Frdy := 96485; Temp := 310; FoRT := Frdy / (R * Temp); Cmem := 1.381E-10; Qpow := (Temp - 310) / 10; cellLength := 100; cellRadius := 10.25; junctionLength := 160E-3; junctionRadius := 15E-3; distSLcyto := 0.45; distJuncSL := 0.5; DcaJuncSL := 1.64E-6; DcaSLcyto := 1.22E-6; DnaJuncSL := 1.09E-5; DnaSLcyto := 1.79E-5; Vcell := pi * power(cellRadius, 2) * cellLength * 1E-15; Vmyo := 0.65 * Vcell; Vsr := 0.035 * Vcell; Vsl := 0.02 * Vcell; Vjunc := 0.0539 * 0.01 * Vcell; SAjunc := 20150 * pi * 2 * junctionLength * junctionRadius; SAsl := pi * 2 * cellRadius * cellLength; J_ca_juncsl := 8.2413E-13; J_ca_slmyo := 3.2743E-12; J_na_juncsl := 1.8313E-14; J_na_slmyo := 1.6386E-12; Fjunc := 0.11; Fsl := 1 - Fjunc; Fjunc_CaL := 0.9; Fsl_CaL := 1 - Fjunc_CaL; Cli := 15; Clo := 150; Ko := 5.4; Nao := 140; Cao := 1.8; Mgi := 1; ena_junc := (1 / FoRT) * ln(Nao / Na_j); ena_sl := (1 / FoRT) * ln(Nao / Na_sl); ek := (1 / FoRT) * ln(Ko / K_i); eca_junc := ((1 / FoRT) / 2) * ln(Cao / Ca_j); eca_sl := ((1 / FoRT) / 2) * ln(Cao / Ca_sl); ecl := (1 / FoRT) * ln(Cli / Clo); GNa := 23; GNaB := 0.597E-3; IbarNaK := 1 * 1.8; KmNaip := 11; KmKo := 1.5; Q10NaK := 1.63; Q10KmNai := 1.39; pNaK := 0.01833; gkp := 2 * 0.001; GClCa := 0.5 * 0.109625; GClB := 1 * 9E-3; KdClCa := 100E-3; pNa := 0.5 * 1.5E-8; pCa := 0.5 * 5.4E-4; pK := 0.5 * 2.7E-7; Q10CaL := 1.8; IbarNCX := 1 * 4.5; KmCai := 3.59E-3; KmCao := 1.3; KmNai := 12.29; KmNao := 87.5; ksat := 0.32; nu := 0.27; Kdact := 0.15E-3; Q10NCX := 1.57; IbarSLCaP := 0.0673; KmPCa := 0.5E-3; GCaB := 5.513E-4; Q10SLCaP := 2.35; Q10SRCaP := 2.6; Vmax_SRCaP := 5.3114E-3; Kmf := 0.246E-3; Kmr := 1.7; hillSRCaP := 1.787; ks := 25; koCa := 10; kom := 0.06; kiCa := 0.5; kim := 0.005; ec50SR := 0.45; Bmax_Naj := 7.561; Bmax_Nasl := 1.65; koff_na := 1E-3; kon_na := 0.1E-3; Bmax_TnClow := 70E-3; koff_tncl := 19.6E-3; kon_tncl := 32.7; Bmax_TnChigh := 140E-3; koff_tnchca := 0.032E-3; kon_tnchca := 2.37; koff_tnchmg := 3.33E-3; kon_tnchmg := 3E-3; Bmax_CaM := 24E-3; koff_cam := 238E-3; kon_cam := 34; Bmax_myosin := 140E-3; koff_myoca := 0.46E-3; kon_myoca := 13.8; koff_myomg := 0.057E-3; kon_myomg := 0.0157; Bmax_SR := 19 * 0.9E-3; koff_sr := 60E-3; kon_sr := 100; Bmax_SLlowsl := (37.4E-3 * Vmyo) / Vsl; Bmax_SLlowj := ((4.6E-3 * Vmyo) / Vjunc) * 0.1; koff_sll := 1300E-3; kon_sll := 100; Bmax_SLhighsl := (13.4E-3 * Vmyo) / Vsl; Bmax_SLhighj := ((1.65E-3 * Vmyo) / Vjunc) * 0.1; koff_slh := 30E-3; kon_slh := 100; Bmax_Csqn := (140E-3 * Vmyo) / Vsr; koff_csqn := 65; kon_csqn := 100; // Variable initializations: Na_j = ; Na_sl = ; K_i = ; Ca_j = ; Ca_sl = ; end model grandi_pasqualini_bers_2010__I_Na(mss, taum, ah, bh, tauh, hss, aj, bj, tauj, jss, m, h, j, I_Na_junc, I_Na_sl, I_Na, V_m, time_, Fjunc, Fsl, GNa, ena_junc, ena_sl) // Assignment Rules: mss := 1 / power(1 + exp(-(56.86 + V_m) / 9.03), 2); taum := 0.1292 * exp(-power((V_m + 45.79) / 15.54, 2)) + 0.06487 * exp(-power((V_m - 4.823) / 51.12, 2)); ah := piecewise( 0 , geq(V_m, -(40)) , 0.057 * exp(-(V_m + 80) / 6.8) ); bh := piecewise( 0.77 / (0.13 * (1 + exp(-(V_m + 10.66) / 11.1))) , geq(V_m, -(40)) , 2.7 * exp(0.079 * V_m) + 3.1E5 * exp(0.3485 * V_m) ); tauh := 1 / (ah + bh); hss := 1 / power(1 + exp((V_m + 71.55) / 7.43), 2); aj := piecewise( 0 , geq(V_m, -(40)) , ((-(2.5428E4) * exp(0.2444 * V_m) - 6.948E-6 * exp(-(0.04391) * V_m)) * (V_m + 37.78)) / (1 + exp(0.311 * (V_m + 79.23))) ); bj := piecewise( (0.6 * exp(0.057 * V_m)) / (1 + exp(-(0.1) * (V_m + 32))) , geq(V_m, -(40)) , (0.02424 * exp(-(0.01052) * V_m)) / (1 + exp(-(0.1378) * (V_m + 40.14))) ); tauj := 1 / (aj + bj); jss := 1 / power(1 + exp((V_m + 71.55) / 7.43), 2); I_Na_junc := Fjunc * GNa * power(m, 3) * h * j * (V_m - ena_junc); I_Na_sl := Fsl * GNa * power(m, 3) * h * j * (V_m - ena_sl); I_Na := I_Na_junc + I_Na_sl; // Rate Rules: m' = (mss - m) / taum; h' = (hss - h) / tauh; j' = (jss - j) / tauj; // Variable initializations: m = 1.405627e-3; h = 9.867005e-1; j = 9.91562e-1; V_m = ; time_ = ; Fjunc = ; Fsl = ; GNa = ; ena_junc = ; ena_sl = ; end model grandi_pasqualini_bers_2010__I_NaBK(I_nabk_junc, I_nabk_sl, I_nabk, V_m, Fjunc, Fsl, GNaB, ena_junc, ena_sl) // Assignment Rules: I_nabk_junc := Fjunc * GNaB * (V_m - ena_junc); I_nabk_sl := Fsl * GNaB * (V_m - ena_sl); I_nabk := I_nabk_junc + I_nabk_sl; // Variable initializations: V_m = ; Fjunc = ; Fsl = ; GNaB = ; ena_junc = ; ena_sl = ; end model grandi_pasqualini_bers_2010__I_NaK(sigma, fnak, I_nak_junc, I_nak_sl, I_nak, V_m, Nao, Ko, FoRT, Fjunc, Fsl, IbarNaK, KmKo, KmNaip, Na_j, Na_sl) // Assignment Rules: sigma := (exp(Nao / 67.3) - 1) / 7; fnak := 1 / (1 + 0.1245 * exp(-(0.1) * V_m * FoRT) + 0.0365 * sigma * exp(- V_m * FoRT)); I_nak_junc := ((Fjunc * IbarNaK * fnak * Ko) / (1 + power(KmNaip / Na_j, 4))) / (Ko + KmKo); I_nak_sl := ((Fsl * IbarNaK * fnak * Ko) / (1 + power(KmNaip / Na_sl, 4))) / (Ko + KmKo); I_nak := I_nak_junc + I_nak_sl; // Variable initializations: V_m = ; Nao = ; Ko = ; FoRT = ; Fjunc = ; Fsl = ; IbarNaK = ; KmKo = ; KmNaip = ; Na_j = ; Na_sl = ; end model grandi_pasqualini_bers_2010__I_Kr(gkr, xrss, tauxr, x_kr, rkr, I_kr, V_m, time_, Ko, ek) // Assignment Rules: gkr := 0.035 * root(Ko / 5.4); xrss := 1 / (1 + exp(-(V_m + 10) / 5)); tauxr := ((550 / (1 + exp((-(22) - V_m) / 9))) * 6) / (1 + exp((V_m - -(11)) / 9)) + 230 / (1 + exp((V_m - -(40)) / 20)); rkr := 1 / (1 + exp((V_m + 74) / 24)); I_kr := gkr * x_kr * rkr * (V_m - ek); // Rate Rules: x_kr' = (xrss - x_kr) / tauxr; // Variable initializations: x_kr = 8.641386e-3; V_m = ; time_ = ; Ko = ; ek = ; end model grandi_pasqualini_bers_2010__I_Kp(kp_kp, I_kp_junc, I_kp_sl, I_kp, V_m, Fjunc, Fsl, ek, gkp) // Assignment Rules: kp_kp := 1 / (1 + exp(7.488 - V_m / 5.98)); I_kp_junc := Fjunc * gkp * kp_kp * (V_m - ek); I_kp_sl := Fsl * gkp * kp_kp * (V_m - ek); I_kp := I_kp_junc + I_kp_sl; // Variable initializations: V_m = ; Fjunc = ; Fsl = ; ek = ; gkp = ; end model grandi_pasqualini_bers_2010__I_Ks(eks, gks_junc, gks_sl, xsss, tauxs, x_ks, I_ks_junc, I_ks_sl, I_ks, V_m, time_, FoRT, Ko, Nao, pNaK, Fjunc, Fsl, K_i, Na_i) // Assignment Rules: eks := (1 / FoRT) * ln((Ko + pNaK * Nao) / (K_i + pNaK * Na_i)); gks_junc := 0.0035; gks_sl := 0.0035; xsss := 1 / (1 + exp(-(V_m + 3.8) / 14.25)); tauxs := 990.1 / (1 + exp(-(V_m + 2.436) / 14.12)); I_ks_junc := Fjunc * gks_junc * power(x_ks, 2) * (V_m - eks); I_ks_sl := Fsl * gks_sl * power(x_ks, 2) * (V_m - eks); I_ks := I_ks_junc + I_ks_sl; // Rate Rules: x_ks' = (xsss - x_ks) / tauxs; // Variable initializations: x_ks = 5.412034e-3; V_m = ; time_ = ; FoRT = ; Ko = ; Nao = ; pNaK = ; Fjunc = ; Fsl = ; K_i = ; Na_i = ; end model grandi_pasqualini_bers_2010__I_to(GtoSlow, GtoFast, xtoss, ytoss, tauxtos, tauytos, x_to_s, y_to_s, I_tos, tauxtof, tauytof, x_to_f, y_to_f, I_tof, I_to, V_m, time_, epi, ek) // Assignment Rules: GtoSlow := piecewise( 1 * 0.13 * 0.12 , epi == 1 , 0.13 * 0.3 * 0.964 ); GtoFast := piecewise( 1 * 0.13 * 0.88 , epi == 1 , 0.13 * 0.3 * 0.036 ); xtoss := 1 / (1 + exp(-(V_m - 19) / 13)); ytoss := 1 / (1 + exp((V_m + 19.5) / 5)); tauxtos := 9 / (1 + exp((V_m + 3) / 15)) + 0.5; tauytos := 800 / (1 + exp((V_m + 60) / 10)) + 30; I_tos := GtoSlow * x_to_s * y_to_s * (V_m - ek); tauxtof := 8.5 * exp(-power((V_m + 45) / 50, 2)) + 0.5; tauytof := 85 * exp(-power(V_m + 40, 2) / 220) + 7; I_tof := GtoFast * x_to_f * y_to_f * (V_m - ek); I_to := I_tos + I_tof; // Rate Rules: x_to_s' = (xtoss - x_to_s) / tauxtos; y_to_s' = (ytoss - y_to_s) / tauytos; x_to_f' = (xtoss - x_to_f) / tauxtof; y_to_f' = (ytoss - y_to_f) / tauytof; // Variable initializations: x_to_s = 4.051574e-3; y_to_s = 9.945511e-1; x_to_f = 4.051574e-3; y_to_f = 9.945511e-1; V_m = ; time_ = ; epi = ; ek = ; end model grandi_pasqualini_bers_2010__I_Ki(aki, bki, kiss, I_ki, V_m, ek, Ko) // Assignment Rules: aki := 1.02 / (1 + exp(0.2385 * ((V_m - ek) - 59.215))); bki := (0.49124 * exp(0.08032 * ((V_m + 5.476) - ek)) + exp(0.06175 * ((V_m - ek) - 594.31))) / (1 + exp(-(0.5143) * ((V_m - ek) + 4.753))); kiss := aki / (aki + bki); I_ki := 1 * 0.35 * root(Ko / 5.4) * kiss * (V_m - ek); // Variable initializations: V_m = ; ek = ; Ko = ; end model grandi_pasqualini_bers_2010__I_ClCa(I_ClCa_junc, I_ClCa_sl, I_ClCa, I_Clbk, V_m, ecl, Fjunc, Fsl, GClCa, GClB, KdClCa, Ca_sl, Ca_j) // Assignment Rules: I_ClCa_junc := ((Fjunc * GClCa) / (1 + KdClCa / Ca_j)) * (V_m - ecl); I_ClCa_sl := ((Fsl * GClCa) / (1 + KdClCa / Ca_sl)) * (V_m - ecl); I_ClCa := I_ClCa_junc + I_ClCa_sl; I_Clbk := GClB * (V_m - ecl); // Variable initializations: V_m = ; ecl = ; Fjunc = ; Fsl = ; GClCa = ; GClB = ; KdClCa = ; Ca_sl = ; Ca_j = ; end model grandi_pasqualini_bers_2010__I_Ca(fss, dss, taud, tauf, d, f, f_Ca_Bj, f_Ca_Bsl, fcaCaMSL, fcaCaj, ibarca_j, ibarca_sl, ibark, ibarna_j, ibarna_sl, I_Ca_junc, I_Ca_sl, I_Ca, I_CaK, I_CaNa_junc, I_CaNa_sl, I_CaNa, I_Catot, V_m, time_, FoRT, Frdy, Fjunc_CaL, Fsl_CaL, Q10CaL, Qpow, pCa, pK, pNa, Cao, Nao, Ko, Ca_j, Ca_sl, Na_j, Na_sl, K_i) // Assignment Rules: fss := 1 / (1 + exp((V_m + 35) / 9)) + 0.6 / (1 + exp((50 - V_m) / 20)); dss := 1 / (1 + exp(-(V_m + 5) / 6)); taud := (1 * dss * (1 - exp(-(V_m + 5) / 6))) / (0.035 * (V_m + 5)); tauf := 1 / (0.0197 * exp(-power(0.0337 * (V_m + 14.5), 2)) + 0.02); fcaCaMSL := 0; fcaCaj := 0; ibarca_j := (pCa * 4 * V_m * Frdy * FoRT * (0.341 * Ca_j * exp(2 * V_m * FoRT) - 0.341 * Cao)) / (exp(2 * V_m * FoRT) - 1); ibarca_sl := (pCa * 4 * V_m * Frdy * FoRT * (0.341 * Ca_sl * exp(2 * V_m * FoRT) - 0.341 * Cao)) / (exp(2 * V_m * FoRT) - 1); ibark := (pK * V_m * Frdy * FoRT * (0.75 * K_i * exp(V_m * FoRT) - 0.75 * Ko)) / (exp(V_m * FoRT) - 1); ibarna_j := (pNa * V_m * Frdy * FoRT * (0.75 * Na_j * exp(V_m * FoRT) - 0.75 * Nao)) / (exp(V_m * FoRT) - 1); ibarna_sl := (pNa * V_m * Frdy * FoRT * (0.75 * Na_sl * exp(V_m * FoRT) - 0.75 * Nao)) / (exp(V_m * FoRT) - 1); I_Ca_junc := Fjunc_CaL * ibarca_j * d * f * ((1 - f_Ca_Bj) + fcaCaj) * power(Q10CaL, Qpow) * 0.45 * 1; I_Ca_sl := Fsl_CaL * ibarca_sl * d * f * ((1 - f_Ca_Bsl) + fcaCaMSL) * power(Q10CaL, Qpow) * 0.45 * 1; I_Ca := I_Ca_junc + I_Ca_sl; I_CaK := ibark * d * f * (Fjunc_CaL * (fcaCaj + (1 - f_Ca_Bj)) + Fsl_CaL * (fcaCaMSL + (1 - f_Ca_Bsl))) * power(Q10CaL, Qpow) * 0.45 * 1; I_CaNa_junc := Fjunc_CaL * ibarna_j * d * f * ((1 - f_Ca_Bj) + fcaCaj) * power(Q10CaL, Qpow) * 0.45 * 1; I_CaNa_sl := Fsl_CaL * ibarna_sl * d * f * ((1 - f_Ca_Bsl) + fcaCaMSL) * power(Q10CaL, Qpow) * 0.45 * 1; I_CaNa := I_CaNa_junc + I_CaNa_sl; I_Catot := I_Ca + I_CaK + I_CaNa; // Rate Rules: d' = (dss - d) / taud; f' = (fss - f) / tauf; f_Ca_Bj' = ((1.7 * Ca_j) / 1) * (1 - f_Ca_Bj) - 11.9E-3 * f_Ca_Bj; f_Ca_Bsl' = ((1.7 * Ca_sl) / 1) * (1 - f_Ca_Bsl) - 11.9E-3 * f_Ca_Bsl; // Variable initializations: d = 7.175662e-6; f = 1.000681; f_Ca_Bj = 2.421991e-2; f_Ca_Bsl = 1.452605e-2; V_m = ; time_ = ; FoRT = ; Frdy = ; Fjunc_CaL = ; Fsl_CaL = ; Q10CaL = ; Qpow = ; pCa = ; pK = ; pNa = ; Cao = ; Nao = ; Ko = ; Ca_j = ; Ca_sl = ; Na_j = ; Na_sl = ; K_i = ; end model grandi_pasqualini_bers_2010__I_NCX(Ka_junc, Ka_sl, s1_junc, s1_sl, s2_junc, s3_junc, s2_sl, s3_sl, I_ncx_junc, I_ncx_sl, I_ncx, V_m, Cao, Nao, FoRT, ksat, Kdact, KmCai, KmCao, KmNai, KmNao, nu, Fjunc, Fsl, IbarNCX, Q10NCX, Qpow, Ca_sl, Ca_j, Na_j, Na_sl) // Assignment Rules: Ka_junc := 1 / (1 + power(Kdact / Ca_j, 2)); Ka_sl := 1 / (1 + power(Kdact / Ca_sl, 2)); s1_junc := exp(nu * V_m * FoRT) * power(Na_j, 3) * Cao; s1_sl := exp(nu * V_m * FoRT) * power(Na_sl, 3) * Cao; s2_junc := exp((nu - 1) * V_m * FoRT) * power(Nao, 3) * Ca_j; s3_junc := KmCai * power(Nao, 3) * (1 + power(Na_j / KmNai, 3)) + power(KmNao, 3) * Ca_j * (1 + Ca_j / KmCai) + KmCao * power(Na_j, 3) + power(Na_j, 3) * Cao + power(Nao, 3) * Ca_j; s2_sl := exp((nu - 1) * V_m * FoRT) * power(Nao, 3) * Ca_sl; s3_sl := KmCai * power(Nao, 3) * (1 + power(Na_sl / KmNai, 3)) + power(KmNao, 3) * Ca_sl * (1 + Ca_sl / KmCai) + KmCao * power(Na_sl, 3) + power(Na_sl, 3) * Cao + power(Nao, 3) * Ca_sl; I_ncx_junc := ((Fjunc * IbarNCX * power(Q10NCX, Qpow) * Ka_junc * (s1_junc - s2_junc)) / s3_junc) / (1 + ksat * exp((nu - 1) * V_m * FoRT)); I_ncx_sl := ((Fsl * IbarNCX * power(Q10NCX, Qpow) * Ka_sl * (s1_sl - s2_sl)) / s3_sl) / (1 + ksat * exp((nu - 1) * V_m * FoRT)); I_ncx := I_ncx_junc + I_ncx_sl; // Variable initializations: V_m = ; Cao = ; Nao = ; FoRT = ; ksat = ; Kdact = ; KmCai = ; KmCao = ; KmNai = ; KmNao = ; nu = ; Fjunc = ; Fsl = ; IbarNCX = ; Q10NCX = ; Qpow = ; Ca_sl = ; Ca_j = ; Na_j = ; Na_sl = ; end model grandi_pasqualini_bers_2010__I_PCa(I_pca_junc, I_pca_sl, I_pca, IbarSLCaP, KmPCa, Fjunc, Fsl, Q10SLCaP, Qpow, Ca_sl, Ca_j) // Assignment Rules: I_pca_junc := (Fjunc * power(Q10SLCaP, Qpow) * IbarSLCaP * power(Ca_j, 1.6)) / (power(KmPCa, 1.6) + power(Ca_j, 1.6)); I_pca_sl := (Fsl * power(Q10SLCaP, Qpow) * IbarSLCaP * power(Ca_sl, 1.6)) / (power(KmPCa, 1.6) + power(Ca_sl, 1.6)); I_pca := I_pca_junc + I_pca_sl; // Variable initializations: IbarSLCaP = ; KmPCa = ; Fjunc = ; Fsl = ; Q10SLCaP = ; Qpow = ; Ca_sl = ; Ca_j = ; end model grandi_pasqualini_bers_2010__I_CaBK(I_cabk_junc, I_cabk_sl, I_cabk, V_m, Fjunc, Fsl, GCaB, eca_junc, eca_sl) // Assignment Rules: I_cabk_junc := Fjunc * GCaB * (V_m - eca_junc); I_cabk_sl := Fsl * GCaB * (V_m - eca_sl); I_cabk := I_cabk_junc + I_cabk_sl; // Variable initializations: V_m = ; Fjunc = ; Fsl = ; GCaB = ; eca_junc = ; eca_sl = ; end model grandi_pasqualini_bers_2010__SR_Fluxes(MaxSR, MinSR, kCaSR, koSRCa, kiSRCa, RI, Ry_Rr, Ry_Ro, Ry_Ri, J_SRCarel, J_serca, J_SRleak, time_, ec50SR, koCa, kiCa, kim, kom, ks, Kmf, Kmr, Q10SRCaP, Qpow, Vmax_SRCaP, hillSRCaP, Ca_sr, Ca_j, Ca_i) // Assignment Rules: MaxSR := 15; MinSR := 1; kCaSR := MaxSR - (MaxSR - MinSR) / (1 + power(ec50SR / Ca_sr, 2.5)); koSRCa := koCa / kCaSR; kiSRCa := kiCa * kCaSR; RI := ((1 - Ry_Rr) - Ry_Ro) - Ry_Ri; J_SRCarel := ((ks * Ry_Ro) / 1) * (Ca_sr - Ca_j); J_serca := (power(Q10SRCaP, Qpow) * Vmax_SRCaP * (power(Ca_i / Kmf, hillSRCaP) - power(Ca_sr / Kmr, hillSRCaP))) / (1 + power(Ca_i / Kmf, hillSRCaP) + power(Ca_sr / Kmr, hillSRCaP)); J_SRleak := 5.348E-6 * (Ca_sr - Ca_j); // Rate Rules: Ry_Rr' = (kim * RI - kiSRCa * Ca_j * Ry_Rr) - (koSRCa * power(Ca_j, 2) * Ry_Rr - kom * Ry_Ro); Ry_Ro' = (koSRCa * power(Ca_j, 2) * Ry_Rr - kom * Ry_Ro) - (kiSRCa * Ca_j * Ry_Ro - kim * Ry_Ri); Ry_Ri' = (kiSRCa * Ca_j * Ry_Ro - kim * Ry_Ri) - (kom * Ry_Ri - koSRCa * power(Ca_j, 2) * RI); // Variable initializations: Ry_Rr = 8.884332e-1; Ry_Ro = 8.156628e-7; Ry_Ri = 1.024274e-7; time_ = ; ec50SR = ; koCa = ; kiCa = ; kim = ; kom = ; ks = ; Kmf = ; Kmr = ; Q10SRCaP = ; Qpow = ; Vmax_SRCaP = ; hillSRCaP = ; Ca_sr = ; Ca_j = ; Ca_i = ; end model grandi_pasqualini_bers_2010__Na_Buffers(Na_Bj, Na_Bsl, dNa_Bj_dt, dNa_Bsl_dt, time_, kon_na, koff_na, Bmax_Naj, Bmax_Nasl, Na_j, Na_sl) // Assignment Rules: dNa_Bj_dt := kon_na * Na_j * (Bmax_Naj - Na_Bj) - koff_na * Na_Bj; dNa_Bsl_dt := kon_na * Na_sl * (Bmax_Nasl - Na_Bsl) - koff_na * Na_Bsl; // Rate Rules: Na_Bj' = dNa_Bj_dt; Na_Bsl' = dNa_Bsl_dt; // Variable initializations: Na_Bj = 3.539892; Na_Bsl = 7.720854e-1; time_ = ; kon_na = ; koff_na = ; Bmax_Naj = ; Bmax_Nasl = ; Na_j = ; Na_sl = ; end model grandi_pasqualini_bers_2010__Cytosolic_Ca_Buffers(Tn_CL, Tn_CHc, Tn_CHm, CaM, Myo_c, Myo_m, SRB, J_CaB_cytosol, time_, Bmax_TnClow, Bmax_CaM, Bmax_TnChigh, Bmax_myosin, Bmax_SR, kon_cam, koff_cam, kon_tncl, koff_tncl, kon_tnchca, koff_tnchca, kon_tnchmg, koff_tnchmg, kon_myomg, koff_myomg, kon_myoca, koff_myoca, kon_sr, koff_sr, Mgi, Ca_i) // Assignment Rules: J_CaB_cytosol := (((((((((((kon_tncl * Ca_i * (Bmax_TnClow - Tn_CL) - koff_tncl * Tn_CL) + kon_tnchca * Ca_i * ((Bmax_TnChigh - Tn_CHc) - Tn_CHm)) - koff_tnchca * Tn_CHc) + kon_tnchmg * Mgi * ((Bmax_TnChigh - Tn_CHc) - Tn_CHm)) - koff_tnchmg * Tn_CHm) + kon_cam * Ca_i * (Bmax_CaM - CaM)) - koff_cam * CaM) + kon_myoca * Ca_i * ((Bmax_myosin - Myo_c) - Myo_m)) - koff_myoca * Myo_c) + kon_myomg * Mgi * ((Bmax_myosin - Myo_c) - Myo_m)) - koff_myomg * Myo_m) + (kon_sr * Ca_i * (Bmax_SR - SRB) - koff_sr * SRB); // Rate Rules: Tn_CL' = kon_tncl * Ca_i * (Bmax_TnClow - Tn_CL) - koff_tncl * Tn_CL; Tn_CHc' = kon_tnchca * Ca_i * ((Bmax_TnChigh - Tn_CHc) - Tn_CHm) - koff_tnchca * Tn_CHc; Tn_CHm' = kon_tnchmg * Mgi * ((Bmax_TnChigh - Tn_CHc) - Tn_CHm) - koff_tnchmg * Tn_CHm; CaM' = kon_cam * Ca_i * (Bmax_CaM - CaM) - koff_cam * CaM; Myo_c' = kon_myoca * Ca_i * ((Bmax_myosin - Myo_c) - Myo_m) - koff_myoca * Myo_c; Myo_m' = kon_myomg * Mgi * ((Bmax_myosin - Myo_c) - Myo_m) - koff_myomg * Myo_m; SRB' = kon_sr * Ca_i * (Bmax_SR - SRB) - koff_sr * SRB; // Variable initializations: Tn_CL = 8.773191e-3; Tn_CHc = 1.078283e-1; Tn_CHm = 1.524002e-2; CaM = 2.911916e-4; Myo_c = 1.298754e-3; Myo_m = 1.381982e-1; SRB = 2.143165e-3; time_ = ; Bmax_TnClow = ; Bmax_CaM = ; Bmax_TnChigh = ; Bmax_myosin = ; Bmax_SR = ; kon_cam = ; koff_cam = ; kon_tncl = ; koff_tncl = ; kon_tnchca = ; koff_tnchca = ; kon_tnchmg = ; koff_tnchmg = ; kon_myomg = ; koff_myomg = ; kon_myoca = ; koff_myoca = ; kon_sr = ; koff_sr = ; Mgi = ; Ca_i = ; end model grandi_pasqualini_bers_2010__Junctional_and_SL_Ca_Buffers(SLL_j, SLL_sl, SLH_j, SLH_sl, J_CaB_junction, J_CaB_sl, time_, Bmax_SLlowj, Bmax_SLlowsl, Bmax_SLhighj, Bmax_SLhighsl, kon_sll, koff_sll, kon_slh, koff_slh, Ca_j, Ca_sl) // Assignment Rules: J_CaB_junction := (kon_sll * Ca_j * (Bmax_SLlowj - SLL_j) - koff_sll * SLL_j) + (kon_slh * Ca_j * (Bmax_SLhighj - SLH_j) - koff_slh * SLH_j); J_CaB_sl := (kon_sll * Ca_sl * (Bmax_SLlowsl - SLL_sl) - koff_sll * SLL_sl) + (kon_slh * Ca_sl * (Bmax_SLhighsl - SLH_sl) - koff_slh * SLH_sl); // Rate Rules: SLL_j' = kon_sll * Ca_j * (Bmax_SLlowj - SLL_j) - koff_sll * SLL_j; SLL_sl' = kon_sll * Ca_sl * (Bmax_SLlowsl - SLL_sl) - koff_sll * SLL_sl; SLH_j' = kon_slh * Ca_j * (Bmax_SLhighj - SLH_j) - koff_slh * SLH_j; SLH_sl' = kon_slh * Ca_sl * (Bmax_SLhighsl - SLH_sl) - koff_slh * SLH_sl; // Variable initializations: SLL_j = 9.566355e-3; SLL_sl = 1.110363e-1; SLH_j = 7.347888e-3; SLH_sl = 7.297378e-2; time_ = ; Bmax_SLlowj = ; Bmax_SLlowsl = ; Bmax_SLhighj = ; Bmax_SLhighsl = ; kon_sll = ; koff_sll = ; kon_slh = ; koff_slh = ; Ca_j = ; Ca_sl = ; end model grandi_pasqualini_bers_2010__SR_Ca_Concentrations(Csqn_b, Ca_sr, time_, Bmax_Csqn, kon_csqn, koff_csqn, Vmyo, Vsr, J_serca, J_SRleak, J_SRCarel) // Rate Rules: Csqn_b' = kon_csqn * Ca_sr * (Bmax_Csqn - Csqn_b) - koff_csqn * Csqn_b; Ca_sr' = (J_serca - ((J_SRleak * Vmyo) / Vsr + J_SRCarel)) - (kon_csqn * Ca_sr * (Bmax_Csqn - Csqn_b) - koff_csqn * Csqn_b); // Variable initializations: Csqn_b = 1.242988; Ca_sr = 0.1e-1; time_ = ; Bmax_Csqn = ; kon_csqn = ; koff_csqn = ; Vmyo = ; Vsr = ; J_serca = ; J_SRleak = ; J_SRCarel = ; end model grandi_pasqualini_bers_2010__Na_Concentrations(I_Na_tot_junc, I_Na_tot_sl, I_Na_tot_sl2, I_Na_tot_junc2, Na_j, Na_sl, Na_i, time_, Cmem, Frdy, J_na_juncsl, J_na_slmyo, Vjunc, Vsl, Vmyo, I_Na_junc, I_nabk_junc, I_ncx_junc, I_nak_junc, I_CaNa_junc, I_Na_sl, I_nabk_sl, I_ncx_sl, I_nak_sl, I_CaNa_sl, dNa_Bj_dt, dNa_Bsl_dt) // Assignment Rules: I_Na_tot_junc := I_Na_junc + I_nabk_junc + 3 * I_ncx_junc + 3 * I_nak_junc + I_CaNa_junc; I_Na_tot_sl := I_Na_sl + I_nabk_sl + 3 * I_ncx_sl + 3 * I_nak_sl + I_CaNa_sl; I_Na_tot_sl2 := 3 * I_ncx_sl + 3 * I_nak_sl + I_CaNa_sl; I_Na_tot_junc2 := 3 * I_ncx_junc + 3 * I_nak_junc + I_CaNa_junc; // Rate Rules: Na_j' = ((- I_Na_tot_junc * Cmem) / (Vjunc * Frdy) + (J_na_juncsl / Vjunc) * (Na_sl - Na_j)) - dNa_Bj_dt; Na_sl' = ((- I_Na_tot_sl * Cmem) / (Vsl * Frdy) + (J_na_juncsl / Vsl) * (Na_j - Na_sl) + (J_na_slmyo / Vsl) * (Na_i - Na_sl)) - dNa_Bsl_dt; Na_i' = (J_na_slmyo / Vmyo) * (Na_sl - Na_i); // Variable initializations: Na_j = 9.06; Na_sl = 9.06; Na_i = 9.06; time_ = ; Cmem = ; Frdy = ; J_na_juncsl = ; J_na_slmyo = ; Vjunc = ; Vsl = ; Vmyo = ; I_Na_junc = ; I_nabk_junc = ; I_ncx_junc = ; I_nak_junc = ; I_CaNa_junc = ; I_Na_sl = ; I_nabk_sl = ; I_ncx_sl = ; I_nak_sl = ; I_CaNa_sl = ; dNa_Bj_dt = ; dNa_Bsl_dt = ; end model grandi_pasqualini_bers_2010__K_Concentration(I_K_tot, K_i, time_, I_to, I_kr, I_ks, I_ki, I_nak, I_CaK, I_kp) // Assignment Rules: I_K_tot := ((I_to + I_kr + I_ks + I_ki) - 2 * I_nak) + I_CaK + I_kp; // Rate Rules: K_i' = 0; // Variable initializations: K_i = 120; time_ = ; I_to = ; I_kr = ; I_ks = ; I_ki = ; I_nak = ; I_CaK = ; I_kp = ; end model grandi_pasqualini_bers_2010__Ca_Concentrations(I_Ca_tot_junc, I_Ca_tot_sl, Ca_j, Ca_sl, Ca_i, time_, I_Ca_junc, I_cabk_junc, I_pca_junc, I_ncx_junc, I_Ca_sl, I_cabk_sl, I_pca_sl, I_ncx_sl, Cmem, Vjunc, Vsl, Vsr, Vmyo, Frdy, J_CaB_junction, J_SRCarel, J_ca_juncsl, J_CaB_sl, J_ca_slmyo, J_serca, J_SRleak, J_CaB_cytosol) // Assignment Rules: I_Ca_tot_junc := (I_Ca_junc + I_cabk_junc + I_pca_junc) - 2 * I_ncx_junc; I_Ca_tot_sl := (I_Ca_sl + I_cabk_sl + I_pca_sl) - 2 * I_ncx_sl; // Rate Rules: Ca_j' = (((- I_Ca_tot_junc * Cmem) / (Vjunc * 2 * Frdy) + (J_ca_juncsl / Vjunc) * (Ca_sl - Ca_j)) - J_CaB_junction) + (J_SRCarel * Vsr) / Vjunc + (J_SRleak * Vmyo) / Vjunc; Ca_sl' = ((- I_Ca_tot_sl * Cmem) / (Vsl * 2 * Frdy) + (J_ca_juncsl / Vsl) * (Ca_j - Ca_sl) + (J_ca_slmyo / Vsl) * (Ca_i - Ca_sl)) - J_CaB_sl; Ca_i' = ((- J_serca * Vsr) / Vmyo - J_CaB_cytosol) + (J_ca_slmyo / Vmyo) * (Ca_sl - Ca_i); // Variable initializations: Ca_j = 1.737475e-4; Ca_sl = 1.031812e-4; Ca_i = 8.597401e-5; time_ = ; I_Ca_junc = ; I_cabk_junc = ; I_pca_junc = ; I_ncx_junc = ; I_Ca_sl = ; I_cabk_sl = ; I_pca_sl = ; I_ncx_sl = ; Cmem = ; Vjunc = ; Vsl = ; Vsr = ; Vmyo = ; Frdy = ; J_CaB_junction = ; J_SRCarel = ; J_ca_juncsl = ; J_CaB_sl = ; J_ca_slmyo = ; J_serca = ; J_SRleak = ; J_CaB_cytosol = ; end model grandi_pasqualini_bers_2010__membrane_potential(V_m, I_app, time_, I_Na_tot_junc, I_Na_tot_sl, I_ClCa, I_Clbk, I_Ca_tot_junc, I_Ca_tot_sl, I_K_tot) // Assignment Rules: I_Na_tot := I_Na_tot_junc + I_Na_tot_sl; I_Cl_tot := I_ClCa + I_Clbk; I_Ca_tot := I_Ca_tot_junc + I_Ca_tot_sl; I_tot := I_Na_tot + I_Cl_tot + I_Ca_tot + I_K_tot; // Rate Rules: V_m' = -(I_tot - I_app); // Variable initializations: V_m = -8.09763e1; I_app = ; time_ = ; I_Na_tot_junc = ; I_Na_tot_sl = ; I_ClCa = ; I_Clbk = ; I_Ca_tot_junc = ; I_Ca_tot_sl = ; I_K_tot = ; end model grandi_pasqualini_bers_2010__interface(time_, V_m, I_app) // Sub-modules, and any changes to those submodules: environment: grandi_pasqualini_bers_2010__environment(time_); parameters: grandi_pasqualini_bers_2010__parameters(epi, R, Frdy, Temp, FoRT, Cmem, Qpow, cellLength, cellRadius, junctionLength, junctionRadius, distSLcyto, distJuncSL, DcaJuncSL, DcaSLcyto, DnaJuncSL, DnaSLcyto, Vcell, Vmyo, Vsr, Vsl, Vjunc, SAjunc, SAsl, J_ca_juncsl, J_ca_slmyo, J_na_juncsl, J_na_slmyo, Fjunc, Fsl, Fjunc_CaL, Fsl_CaL, Cli, Clo, Ko, Nao, Cao, Mgi, ena_junc, ena_sl, ek, eca_junc, eca_sl, ecl, GNa, GNaB, IbarNaK, KmNaip, KmKo, Q10NaK, Q10KmNai, pNaK, gkp, GClCa, GClB, KdClCa, pNa, pCa, pK, Q10CaL, IbarNCX, KmCai, KmCao, KmNai, KmNao, ksat, nu, Kdact, Q10NCX, IbarSLCaP, KmPCa, GCaB, Q10SLCaP, Q10SRCaP, Vmax_SRCaP, Kmf, Kmr, hillSRCaP, ks, koCa, kom, kiCa, kim, ec50SR, Bmax_Naj, Bmax_Nasl, koff_na, kon_na, Bmax_TnClow, koff_tncl, kon_tncl, Bmax_TnChigh, koff_tnchca, kon_tnchca, koff_tnchmg, kon_tnchmg, Bmax_CaM, koff_cam, kon_cam, Bmax_myosin, koff_myoca, kon_myoca, koff_myomg, kon_myomg, Bmax_SR, koff_sr, kon_sr, Bmax_SLlowsl, Bmax_SLlowj, koff_sll, kon_sll, Bmax_SLhighsl, Bmax_SLhighj, koff_slh, kon_slh, Bmax_Csqn, koff_csqn, kon_csqn, Na_j, Na_sl, K_i, Ca_j, Ca_sl); I_Na: grandi_pasqualini_bers_2010__I_Na(mss, taum, ah, bh, tauh, hss, aj, bj, tauj, jss, m, h, j, I_Na_junc, I_Na_sl, I_Na0, V_m, time_, Fjunc, Fsl, GNa, ena_junc, ena_sl); I_NaBK: grandi_pasqualini_bers_2010__I_NaBK(I_nabk_junc, I_nabk_sl, I_nabk, V_m, Fjunc, Fsl, GNaB, ena_junc, ena_sl); I_NaK: grandi_pasqualini_bers_2010__I_NaK(sigma, fnak, I_nak_junc, I_nak_sl, I_nak, V_m, Nao, Ko, FoRT, Fjunc, Fsl, IbarNaK, KmKo, KmNaip, Na_j, Na_sl); I_Kr: grandi_pasqualini_bers_2010__I_Kr(gkr, xrss, tauxr, x_kr, rkr, I_kr, V_m, time_, Ko, ek); I_Kp: grandi_pasqualini_bers_2010__I_Kp(kp_kp, I_kp_junc, I_kp_sl, I_kp, V_m, Fjunc, Fsl, ek, gkp); I_Ks: grandi_pasqualini_bers_2010__I_Ks(eks, gks_junc, gks_sl, xsss, tauxs, x_ks, I_ks_junc, I_ks_sl, I_ks, V_m, time_, FoRT, Ko, Nao, pNaK, Fjunc, Fsl, K_i, Na_i); I_to: grandi_pasqualini_bers_2010__I_to(GtoSlow, GtoFast, xtoss, ytoss, tauxtos, tauytos, x_to_s, y_to_s, I_tos, tauxtof, tauytof, x_to_f, y_to_f, I_tof, I_to0, V_m, time_, epi, ek); I_Ki: grandi_pasqualini_bers_2010__I_Ki(aki, bki, kiss, I_ki, V_m, ek, Ko); I_ClCa: grandi_pasqualini_bers_2010__I_ClCa(I_ClCa_junc, I_ClCa_sl, I_ClCa0, I_Clbk, V_m, ecl, Fjunc, Fsl, GClCa, GClB, KdClCa, Ca_sl, Ca_j); I_Ca: grandi_pasqualini_bers_2010__I_Ca(fss, dss, taud, tauf, d, f, f_Ca_Bj, f_Ca_Bsl, fcaCaMSL, fcaCaj, ibarca_j, ibarca_sl, ibark, ibarna_j, ibarna_sl, I_Ca_junc, I_Ca_sl, I_Ca0, I_CaK, I_CaNa_junc, I_CaNa_sl, I_CaNa, I_Catot, V_m, time_, FoRT, Frdy, Fjunc_CaL, Fsl_CaL, Q10CaL, Qpow, pCa, pK, pNa, Cao, Nao, Ko, Ca_j, Ca_sl, Na_j, Na_sl, K_i); I_NCX: grandi_pasqualini_bers_2010__I_NCX(Ka_junc, Ka_sl, s1_junc, s1_sl, s2_junc, s3_junc, s2_sl, s3_sl, I_ncx_junc, I_ncx_sl, I_ncx, V_m, Cao, Nao, FoRT, ksat, Kdact, KmCai, KmCao, KmNai, KmNao, nu, Fjunc, Fsl, IbarNCX, Q10NCX, Qpow, Ca_sl, Ca_j, Na_j, Na_sl); I_PCa: grandi_pasqualini_bers_2010__I_PCa(I_pca_junc, I_pca_sl, I_pca, IbarSLCaP, KmPCa, Fjunc, Fsl, Q10SLCaP, Qpow, Ca_sl, Ca_j); I_CaBK: grandi_pasqualini_bers_2010__I_CaBK(I_cabk_junc, I_cabk_sl, I_cabk, V_m, Fjunc, Fsl, GCaB, eca_junc, eca_sl); SR_Fluxes: grandi_pasqualini_bers_2010__SR_Fluxes(MaxSR, MinSR, kCaSR, koSRCa, kiSRCa, RI, Ry_Rr, Ry_Ro, Ry_Ri, J_SRCarel, J_serca, J_SRleak, time_, ec50SR, koCa, kiCa, kim, kom, ks, Kmf, Kmr, Q10SRCaP, Qpow, Vmax_SRCaP, hillSRCaP, Ca_sr, Ca_j, Ca_i); Na_Buffers: grandi_pasqualini_bers_2010__Na_Buffers(Na_Bj, Na_Bsl, dNa_Bj_dt, dNa_Bsl_dt, time_, kon_na, koff_na, Bmax_Naj, Bmax_Nasl, Na_j, Na_sl); Cytosolic_Ca_Buffers: grandi_pasqualini_bers_2010__Cytosolic_Ca_Buffers(Tn_CL, Tn_CHc, Tn_CHm, CaM, Myo_c, Myo_m, SRB, J_CaB_cytosol, time_, Bmax_TnClow, Bmax_CaM, Bmax_TnChigh, Bmax_myosin, Bmax_SR, kon_cam, koff_cam, kon_tncl, koff_tncl, kon_tnchca, koff_tnchca, kon_tnchmg, koff_tnchmg, kon_myomg, koff_myomg, kon_myoca, koff_myoca, kon_sr, koff_sr, Mgi, Ca_i); Junctional_and_SL_Ca_Buffers: grandi_pasqualini_bers_2010__Junctional_and_SL_Ca_Buffers(SLL_j, SLL_sl, SLH_j, SLH_sl, J_CaB_junction, J_CaB_sl, time_, Bmax_SLlowj, Bmax_SLlowsl, Bmax_SLhighj, Bmax_SLhighsl, kon_sll, koff_sll, kon_slh, koff_slh, Ca_j, Ca_sl); SR_Ca_Concentrations: grandi_pasqualini_bers_2010__SR_Ca_Concentrations(Csqn_b, Ca_sr, time_, Bmax_Csqn, kon_csqn, koff_csqn, Vmyo, Vsr, J_serca, J_SRleak, J_SRCarel); Na_Concentrations: grandi_pasqualini_bers_2010__Na_Concentrations(I_Na_tot_junc, I_Na_tot_sl, I_Na_tot_sl2, I_Na_tot_junc2, Na_j, Na_sl, Na_i, time_, Cmem, Frdy, J_na_juncsl, J_na_slmyo, Vjunc, Vsl, Vmyo, I_Na_junc, I_nabk_junc, I_ncx_junc, I_nak_junc, I_CaNa_junc, I_Na_sl, I_nabk_sl, I_ncx_sl, I_nak_sl, I_CaNa_sl, dNa_Bj_dt, dNa_Bsl_dt); K_Concentration: grandi_pasqualini_bers_2010__K_Concentration(I_K_tot, K_i, time_, I_to0, I_kr, I_ks, I_ki, I_nak, I_CaK, I_kp); Ca_Concentrations: grandi_pasqualini_bers_2010__Ca_Concentrations(I_Ca_tot_junc, I_Ca_tot_sl, Ca_j, Ca_sl, Ca_i, time_, I_Ca_junc, I_cabk_junc, I_pca_junc, I_ncx_junc, I_Ca_sl, I_cabk_sl, I_pca_sl, I_ncx_sl, Cmem, Vjunc, Vsl, Vsr, Vmyo, Frdy, J_CaB_junction, J_SRCarel, J_ca_juncsl, J_CaB_sl, J_ca_slmyo, J_serca, J_SRleak, J_CaB_cytosol); membrane_potential: grandi_pasqualini_bers_2010__membrane_potential(V_m, I_app, time_, I_Na_tot_junc, I_Na_tot_sl, I_ClCa0, I_Clbk, I_Ca_tot_junc, I_Ca_tot_sl, I_K_tot); end model *grandi_pasqualini_bers_2010____main() // Sub-modules, and any changes to those submodules: interface: grandi_pasqualini_bers_2010__interface(time_, V_m, I_app); end