//Created by libAntimony v2.4 // Warnings from automatic translation: // Unable to use the formula "(C1 * beta + C_Ca0 * omega) - (C0 * 4.0 * alpha + C0 * gamma)" to set the assignment rule for C0: Loop detected: C0's definition ((C1 * beta + C_Ca0 * omega) - (C0 * 4.0 * alpha + C0 * gamma)) either includes itself directly (i.e. 's5 := 6 + s5') or by proxy (i.e. 's5 := 8*d3' and 'd3 := 9*s5'). // Unable to use the formula "(C0 * 4.0 * alpha + C2 * 2.0 * beta + C_Ca1 * (omega / b)) - (C1 * beta + C1 * 3.0 * alpha + C1 * gamma * a)" to set the assignment rule for C1: Loop detected: C1's definition ((C0 * 4.0 * alpha + C2 * 2.0 * beta + C_Ca1 * (omega / b)) - (C1 * beta + C1 * 3.0 * alpha + C1 * gamma * a)) either includes itself directly (i.e. 's5 := 6 + s5') or by proxy (i.e. 's5 := 8*d3' and 'd3 := 9*s5'). // Unable to use the formula "(C1 * 3.0 * alpha + C3 * 3.0 * beta + C_Ca2 * (omega / power(b, 2.0))) - (C2 * 2.0 * beta + C2 * 2.0 * alpha + C2 * gamma * power(a, 2.0))" to set the assignment rule for C2: Loop detected: C2's definition ((C1 * 3.0 * alpha + C3 * 3.0 * beta + C_Ca2 * (omega / power(b, 2.0))) - (C2 * 2.0 * beta + C2 * 2.0 * alpha + C2 * gamma * power(a, 2.0))) either includes itself directly (i.e. 's5 := 6 + s5') or by proxy (i.e. 's5 := 8*d3' and 'd3 := 9*s5'). // Unable to use the formula "(C2 * 2.0 * alpha + C4 * 4.0 * beta + C_Ca3 * (omega / power(b, 3.0))) - (C3 * 3.0 * beta + C3 * alpha + C3 * gamma * power(a, 3.0))" to set the assignment rule for C3: Loop detected: C3's definition ((C2 * 2.0 * alpha + C4 * 4.0 * beta + C_Ca3 * (omega / power(b, 3.0))) - (C3 * 3.0 * beta + C3 * alpha + C3 * gamma * power(a, 3.0))) either includes itself directly (i.e. 's5 := 6 + s5') or by proxy (i.e. 's5 := 8*d3' and 'd3 := 9*s5'). // Unable to use the formula "(C3 * alpha + O * g + C_Ca4 * (omega / power(b, 4.0))) - (C4 * 4.0 * beta + C4 * f + C4 * gamma * power(a, 4.0))" to set the assignment rule for C4: Loop detected: C4's definition ((C3 * alpha + O * g + C_Ca4 * (omega / power(b, 4.0))) - (C4 * 4.0 * beta + C4 * f + C4 * gamma * power(a, 4.0))) either includes itself directly (i.e. 's5 := 6 + s5') or by proxy (i.e. 's5 := 8*d3' and 'd3 := 9*s5'). // Unable to use the formula "C4 * f - O * g" to set the assignment rule for O: Loop detected: O's definition (C4 * f - O * g) either includes itself directly (i.e. 's5 := 6 + s5') or by proxy (i.e. 's5 := 8*d3' and 'd3 := 9*s5'). // Unable to use the formula "(C0 * gamma + C_Ca1 * beta_) - (C_Ca0 * 4.0 * alpha_ + C_Ca0 * omega)" to set the assignment rule for C_Ca0: Loop detected: C_Ca0's definition ((C0 * gamma + C_Ca1 * beta_) - (C_Ca0 * 4.0 * alpha_ + C_Ca0 * omega)) either includes itself directly (i.e. 's5 := 6 + s5') or by proxy (i.e. 's5 := 8*d3' and 'd3 := 9*s5'). // Unable to use the formula "(C_Ca0 * 4.0 * alpha_ + C_Ca2 * 2.0 * beta_ + C1 * gamma * a) - (C_Ca1 * beta_ + C_Ca1 * 3.0 * alpha_ + C_Ca1 * (omega / b))" to set the assignment rule for C_Ca1: Loop detected: C_Ca1's definition ((C_Ca0 * 4.0 * alpha_ + C_Ca2 * 2.0 * beta_ + C1 * gamma * a) - (C_Ca1 * beta_ + C_Ca1 * 3.0 * alpha_ + C_Ca1 * (omega / b))) either includes itself directly (i.e. 's5 := 6 + s5') or by proxy (i.e. 's5 := 8*d3' and 'd3 := 9*s5'). // Unable to use the formula "(C_Ca1 * 3.0 * alpha_ + C_Ca3 * 3.0 * beta_ + C2 * gamma * power(a, 2.0)) - (C_Ca2 * 2.0 * beta_ + C_Ca2 * 2.0 * alpha_ + C_Ca2 * (omega / power(b, 2.0)))" to set the assignment rule for C_Ca2: Loop detected: C_Ca2's definition ((C_Ca1 * 3.0 * alpha_ + C_Ca3 * 3.0 * beta_ + C2 * gamma * power(a, 2.0)) - (C_Ca2 * 2.0 * beta_ + C_Ca2 * 2.0 * alpha_ + C_Ca2 * (omega / power(b, 2.0)))) either includes itself directly (i.e. 's5 := 6 + s5') or by proxy (i.e. 's5 := 8*d3' and 'd3 := 9*s5'). // Unable to use the formula "(C_Ca2 * 2.0 * alpha_ + C_Ca4 * 4.0 * beta_ + C3 * gamma * power(a, 3.0)) - (C_Ca3 * 3.0 * beta_ + C_Ca3 * alpha_ + C_Ca3 * (omega / power(b, 3.0)))" to set the assignment rule for C_Ca3: Loop detected: C_Ca3's definition ((C_Ca2 * 2.0 * alpha_ + C_Ca4 * 4.0 * beta_ + C3 * gamma * power(a, 3.0)) - (C_Ca3 * 3.0 * beta_ + C_Ca3 * alpha_ + C_Ca3 * (omega / power(b, 3.0)))) either includes itself directly (i.e. 's5 := 6 + s5') or by proxy (i.e. 's5 := 8*d3' and 'd3 := 9*s5'). // Unable to use the formula "(C_Ca3 * alpha_ + O_Ca * g_ + C4 * gamma * power(a, 4.0)) - (C_Ca4 * 4.0 * beta_ + C_Ca4 * f_ + C_Ca4 * (omega / power(b, 4.0)))" to set the assignment rule for C_Ca4: Loop detected: C_Ca4's definition ((C_Ca3 * alpha_ + O_Ca * g_ + C4 * gamma * power(a, 4.0)) - (C_Ca4 * 4.0 * beta_ + C_Ca4 * f_ + C_Ca4 * (omega / power(b, 4.0)))) either includes itself directly (i.e. 's5 := 6 + s5') or by proxy (i.e. 's5 := 8*d3' and 'd3 := 9*s5'). // Unable to use the formula "C_Ca4 * f_ - O_Ca * g_" to set the assignment rule for O_Ca: Loop detected: O_Ca's definition (C_Ca4 * f_ - O_Ca * g_) either includes itself directly (i.e. 's5 := 6 + s5') or by proxy (i.e. 's5 := 8*d3' and 'd3 := 9*s5'). // Unable to use the formula "P_C2 * k21 - P_C1 * k12" to set the assignment rule for P_C1: Loop detected: P_C1's definition (P_C2 * k21 - P_C1 * k12) either includes itself directly (i.e. 's5 := 6 + s5') or by proxy (i.e. 's5 := 8*d3' and 'd3 := 9*s5'). // Unable to use the formula "(P_C1 * k12 + P_O3 * k32 + P_C5 * k52) - (P_C2 * k21 + P_C2 * k23 + P_C2 * k25)" to set the assignment rule for P_C2: Loop detected: P_C2's definition ((P_C1 * k12 + P_O3 * k32 + P_C5 * k52) - (P_C2 * k21 + P_C2 * k23 + P_C2 * k25)) either includes itself directly (i.e. 's5 := 6 + s5') or by proxy (i.e. 's5 := 8*d3' and 'd3 := 9*s5'). // Unable to use the formula "(P_C2 * k23 + P_O4 * k43) - (P_O3 * k32 + P_O3 * k34)" to set the assignment rule for P_O3: Loop detected: P_O3's definition ((P_C2 * k23 + P_O4 * k43) - (P_O3 * k32 + P_O3 * k34)) either includes itself directly (i.e. 's5 := 6 + s5') or by proxy (i.e. 's5 := 8*d3' and 'd3 := 9*s5'). // Unable to use the formula "(P_O3 * k34 + P_C5 * k54) - (P_O4 * k43 + P_O4 * k45)" to set the assignment rule for P_O4: Loop detected: P_O4's definition ((P_O3 * k34 + P_C5 * k54) - (P_O4 * k43 + P_O4 * k45)) either includes itself directly (i.e. 's5 := 6 + s5') or by proxy (i.e. 's5 := 8*d3' and 'd3 := 9*s5'). // Unable to use the formula "(P_C2 * k25 + P_O4 * k45 + P_C6 * k65) - (P_C5 * k52 + P_C5 * k54 + P_C5 * k56)" to set the assignment rule for P_C5: Loop detected: P_C5's definition ((P_C2 * k25 + P_O4 * k45 + P_C6 * k65) - (P_C5 * k52 + P_C5 * k54 + P_C5 * k56)) either includes itself directly (i.e. 's5 := 6 + s5') or by proxy (i.e. 's5 := 8*d3' and 'd3 := 9*s5'). // Unable to use the formula "P_C6 * k65 - P_C5 * k56" to set the assignment rule for P_C6: Loop detected: P_C6's definition (P_C6 * k65 - P_C5 * k56) either includes itself directly (i.e. 's5 := 6 + s5') or by proxy (i.e. 's5 := 8*d3' and 'd3 := 9*s5'). model rice_winslow_jafri_1999_version01__environment(time_) // Variable initializations: time_ = ; end model rice_winslow_jafri_1999_version01__sarcolemma(V, R, T, F, Ca_o) // Variable initializations: V = -84.624; R = 8.314; T = 310.0; F = 96500.0; Ca_o = 1.8; end model rice_winslow_jafri_1999_version01__subspace(V_SS, J_RyR, Ca_SS, V, time_, R, T, F, Ca_o, O, O_Ca, P_O3, P_O4, Ca_JSR) // Assignment Rules: J_RyR := sum(J_RyR_perm * RyR_open * (Ca_JSR - Ca_SS)); J_DHPR := (I_DHPR * DHPR_open) / (2.0 * F * V_SS); DHPR_open := piecewise( 1.0 , ( (i == O)) || ((i == O_Ca) ), 0.0 ); RyR_open := piecewise( 1.0 , ( (i == P_O3)) || ((i == P_O4) ), 0.0 ); I_DHPR := P_Ca * 4.0 * ((V * power(F, 2.0)) / (R * T)) * ((0.001 * exp((2.0 * V * F) / (R * T)) - 0.341 * Ca_o) / (exp((2.0 * V * F) / (R * T)) - 1.0)); beta_SS := power(1.0 + (B_SR * K_BSR) / power(K_BSR + Ca_SS, 2.0) + (B_SL * K_BSL) / power(K_BSL + Ca_SS, 2.0), -1.0); J_xfer := (1.0 / tau_xfer) * (Ca_SS - Ca_myo); // Rate Rules: Ca_SS' = beta_SS * (J_DHPR + J_RyR + (V_myo / V_SS) * J_xfer); // Variable initializations: V_SS = 2.03E-12; Ca_SS = ; J_RyR_perm = 3960.0; B_SR = 47.0; K_BSR = 0.87; B_SL = 1124.0; K_BSL = 8.7; P_Ca = 1.51E-11; tau_xfer = 0.0007; Ca_myo = 0.1; i = 0.0; V_myo = 0.1; V = ; time_ = ; R = ; T = ; F = ; Ca_o = ; O = ; O_Ca = ; P_O3 = ; P_O4 = ; Ca_JSR = ; sum = ; end model rice_winslow_jafri_1999_version01__sarcoplasmic_reticulum(Ca_JSR, J_RyR, V_SS, time_) // Assignment Rules: beta_JSR := power(1.0 + (CSQN_tot * K_CSQN) / power(K_CSQN + Ca_JSR, 2.0), -1.0); J_tr := (1.0 / tau_tr) * (Ca_NSR - Ca_JSR); // Rate Rules: Ca_JSR' = beta_JSR * (J_tr - (V_SS / V_JSR) * J_RyR); // Variable initializations: Ca_JSR = ; V_JSR = 2.03E-12; CSQN_tot = 15.0; K_CSQN = 0.8; tau_tr = 0.005; Ca_NSR = 800.0; J_RyR = ; V_SS = ; time_ = ; end model rice_winslow_jafri_1999_version01__C0(C0, C1, C_Ca0, alpha, beta, omega, gamma) // Variable initializations: C0 = ; C1 = ; C_Ca0 = ; alpha = ; beta = ; omega = ; gamma = ; end model rice_winslow_jafri_1999_version01__C1(C1, C0, C2, C_Ca1, alpha, beta, omega, gamma, a, b) // Variable initializations: C1 = ; C0 = ; C2 = ; C_Ca1 = ; alpha = ; beta = ; omega = ; gamma = ; a = ; b = ; end model rice_winslow_jafri_1999_version01__C2(C2, C1, C3, C_Ca2, alpha, beta, omega, gamma, a, b) // Variable initializations: C2 = ; C1 = ; C3 = ; C_Ca2 = ; alpha = ; beta = ; omega = ; gamma = ; a = ; b = ; end model rice_winslow_jafri_1999_version01__C3(C3, C2, C4, C_Ca3, alpha, beta, omega, gamma, a, b) // Variable initializations: C3 = ; C2 = ; C4 = ; C_Ca3 = ; alpha = ; beta = ; omega = ; gamma = ; a = ; b = ; end model rice_winslow_jafri_1999_version01__C4(C4, C3, O, C_Ca4, alpha, beta, omega, gamma, a, b, f, g) // Variable initializations: C4 = ; C3 = ; O = ; C_Ca4 = ; alpha = ; beta = ; omega = ; gamma = ; a = ; b = ; f = ; g = ; end model rice_winslow_jafri_1999_version01__O(O, C4, f, g) // Variable initializations: O = ; C4 = ; f = ; g = ; end model rice_winslow_jafri_1999_version01__C_Ca0(C_Ca0, C0, C_Ca1, alpha_, beta_, omega, gamma) // Variable initializations: C_Ca0 = ; C0 = ; C_Ca1 = ; alpha_ = ; beta_ = ; omega = ; gamma = ; end model rice_winslow_jafri_1999_version01__C_Ca1(C_Ca1, C_Ca0, C_Ca2, C1, alpha_, beta_, omega, gamma, a, b) // Variable initializations: C_Ca1 = ; C_Ca0 = ; C_Ca2 = ; C1 = ; alpha_ = ; beta_ = ; omega = ; gamma = ; a = ; b = ; end model rice_winslow_jafri_1999_version01__C_Ca2(C_Ca2, C_Ca1, C_Ca3, C2, alpha_, beta_, omega, gamma, a, b) // Variable initializations: C_Ca2 = ; C_Ca1 = ; C_Ca3 = ; C2 = ; alpha_ = ; beta_ = ; omega = ; gamma = ; a = ; b = ; end model rice_winslow_jafri_1999_version01__C_Ca3(C_Ca3, C_Ca2, C_Ca4, C3, alpha_, beta_, omega, gamma, a, b) // Variable initializations: C_Ca3 = ; C_Ca2 = ; C_Ca4 = ; C3 = ; alpha_ = ; beta_ = ; omega = ; gamma = ; a = ; b = ; end model rice_winslow_jafri_1999_version01__C_Ca4(C_Ca4, C_Ca3, O_Ca, C4, alpha_, beta_, omega, gamma, a, b, f_, g_) // Variable initializations: C_Ca4 = ; C_Ca3 = ; O_Ca = ; C4 = ; alpha_ = ; beta_ = ; omega = ; gamma = ; a = ; b = ; f_ = ; g_ = ; end model rice_winslow_jafri_1999_version01__O_Ca(O_Ca, C_Ca4, f_, g_) // Variable initializations: O_Ca = ; C_Ca4 = ; f_ = ; g_ = ; end model rice_winslow_jafri_1999_version01__P_C1(P_C1, k12, k21, P_C2) // Variable initializations: P_C1 = ; k12 = ; k21 = ; P_C2 = ; end model rice_winslow_jafri_1999_version01__P_C2(P_C2, k12, k21, k23, k32, k25, k52, P_C1, P_O3, P_C5) // Variable initializations: P_C2 = ; k12 = ; k21 = ; k23 = ; k32 = ; k25 = ; k52 = ; P_C1 = ; P_O3 = ; P_C5 = ; end model rice_winslow_jafri_1999_version01__P_O3(P_O3, k23, k32, k34, k43, P_C2, P_O4) // Variable initializations: P_O3 = ; k23 = ; k32 = ; k34 = ; k43 = ; P_C2 = ; P_O4 = ; end model rice_winslow_jafri_1999_version01__P_O4(P_O4, k45, k54, k34, k43, P_C5, P_O3) // Variable initializations: P_O4 = ; k45 = ; k54 = ; k34 = ; k43 = ; P_C5 = ; P_O3 = ; end model rice_winslow_jafri_1999_version01__P_C5(P_C5, k45, k54, k56, k65, k25, k52, P_C2, P_O4, P_C6) // Variable initializations: P_C5 = ; k45 = ; k54 = ; k56 = ; k65 = ; k25 = ; k52 = ; P_C2 = ; P_O4 = ; P_C6 = ; end model rice_winslow_jafri_1999_version01__P_C6(P_C6, k56, k65, P_C5) // Variable initializations: P_C6 = ; k56 = ; k65 = ; P_C5 = ; end model rice_winslow_jafri_1999_version01__DHPR_transition_probabilities(alpha, gamma, beta, alpha_, beta_, omega, a, b, f, g, f_, g_, V, Ca_SS) // Assignment Rules: alpha := 0.4 * exp((V + 6.0) / 25.0); gamma := Ca_SS * 0.1875; beta := 0.05 * exp(-(V + 6.0) / 29.0); alpha_ := alpha * a; beta_ := beta / b; // Variable initializations: omega = 10.0; a = 2.0; b = 2.0; f = 300.0; g = 2000.0; f_ = 5.0; g_ = 7000.0; V = ; Ca_SS = ; end model rice_winslow_jafri_1999_version01__RyR_transition_probabilities(k12, k21, k23, k32, k34, k43, k54, k45, k25, k52, k56, k65, Ca_SS) // Assignment Rules: k12 := (3.0E6 * power(Ca_SS, 4.0)) / (power(2.68, 4.0) + power(Ca_SS, 4.0)); k23 := (3.0E7 * power(Ca_SS, 4.0)) / (power(2.68, 4.0) + power(Ca_SS, 4.0)); k34 := (3.0E6 * power(Ca_SS, 4.0)) / (power(2.68, 4.0) + power(Ca_SS, 4.0)); k54 := (198.0 * power(Ca_SS, 4.0)) / (power(2.68, 4.0) + power(Ca_SS, 4.0)); k25 := (3.0E5 * power(Ca_SS, 4.0)) / (power(2.68, 4.0) + power(Ca_SS, 4.0)); k56 := (3.0E6 * power(Ca_SS, 4.0)) / (power(2.68, 4.0) + power(Ca_SS, 4.0)); // Variable initializations: k21 = 2.5E5; k32 = 9.6E3; k43 = 1.3E4; k45 = 66.67; k52 = 1.235; k65 = 3.0E6; Ca_SS = ; end model *rice_winslow_jafri_1999_version01____main() // Sub-modules, and any changes to those submodules: environment: rice_winslow_jafri_1999_version01__environment(time_); sarcolemma: rice_winslow_jafri_1999_version01__sarcolemma(V, R, T, F, Ca_o); subspace: rice_winslow_jafri_1999_version01__subspace(V_SS, J_RyR, Ca_SS, V, time_, R, T, F, Ca_o, O0, O_Ca0, P_O30, P_O40, Ca_JSR); sarcoplasmic_reticulum: rice_winslow_jafri_1999_version01__sarcoplasmic_reticulum(Ca_JSR, J_RyR, V_SS, time_); C0: rice_winslow_jafri_1999_version01__C0(C00, C10, C_Ca00, alpha, beta, omega, gamma); C1: rice_winslow_jafri_1999_version01__C1(C10, C00, C20, C_Ca10, alpha, beta, omega, gamma, a, b); C2: rice_winslow_jafri_1999_version01__C2(C20, C10, C30, C_Ca20, alpha, beta, omega, gamma, a, b); C3: rice_winslow_jafri_1999_version01__C3(C30, C20, C40, C_Ca30, alpha, beta, omega, gamma, a, b); C4: rice_winslow_jafri_1999_version01__C4(C40, C30, O0, C_Ca40, alpha, beta, omega, gamma, a, b, f, g); O: rice_winslow_jafri_1999_version01__O(O0, C40, f, g); C_Ca0: rice_winslow_jafri_1999_version01__C_Ca0(C_Ca00, C00, C_Ca10, alpha_, beta_, omega, gamma); C_Ca1: rice_winslow_jafri_1999_version01__C_Ca1(C_Ca10, C_Ca00, C_Ca20, C10, alpha_, beta_, omega, gamma, a, b); C_Ca2: rice_winslow_jafri_1999_version01__C_Ca2(C_Ca20, C_Ca10, C_Ca30, C20, alpha_, beta_, omega, gamma, a, b); C_Ca3: rice_winslow_jafri_1999_version01__C_Ca3(C_Ca30, C_Ca20, C_Ca40, C30, alpha_, beta_, omega, gamma, a, b); C_Ca4: rice_winslow_jafri_1999_version01__C_Ca4(C_Ca40, C_Ca30, O_Ca0, C40, alpha_, beta_, omega, gamma, a, b, f_, g_); O_Ca: rice_winslow_jafri_1999_version01__O_Ca(O_Ca0, C_Ca40, f_, g_); P_C1: rice_winslow_jafri_1999_version01__P_C1(P_C10, k12, k21, P_C20); P_C2: rice_winslow_jafri_1999_version01__P_C2(P_C20, k12, k21, k23, k32, k25, k52, P_C10, P_O30, P_C50); P_O3: rice_winslow_jafri_1999_version01__P_O3(P_O30, k23, k32, k34, k43, P_C20, P_O40); P_O4: rice_winslow_jafri_1999_version01__P_O4(P_O40, k45, k54, k34, k43, P_C50, P_O30); P_C5: rice_winslow_jafri_1999_version01__P_C5(P_C50, k45, k54, k56, k65, k25, k52, P_C20, P_O40, P_C60); P_C6: rice_winslow_jafri_1999_version01__P_C6(P_C60, k56, k65, P_C50); DHPR_transition_probabilities: rice_winslow_jafri_1999_version01__DHPR_transition_probabilities(alpha, gamma, beta, alpha_, beta_, omega, a, b, f, g, f_, g_, V, Ca_SS); RyR_transition_probabilities: rice_winslow_jafri_1999_version01__RyR_transition_probabilities(k12, k21, k23, k32, k34, k43, k54, k45, k25, k52, k56, k65, Ca_SS); end