//Created by libAntimony v2.4 // Warnings from automatic translation: // Unable to use the formula "pi * preplength * power(radius, 2)" to set the assignment rule for volume: The variable 'volume' is the type Unit Definition, and may not have an assignment rule associated with it. model clancy_rudy_2001_version01__environment(time_) // Variable initializations: time_ = ; end model clancy_rudy_2001_version01__membrane(V, R, T, F, time_, i_Na, i_Ca_L, i_Ca_T, i_Kr, i_Ks, i_K_Na, i_K_ATP, i_to, i_NaCa, i_K1, i_Kp, i_p_Ca, i_Na_b, i_Ca_b, i_NaK, i_ns_Ca, dVdt) // Assignment Rules: I_st := piecewise( stim_amplitude , (( geq(time_, stim_start)) && (time_ <= stim_end) && ((time_ - stim_start) - floor((time_ - stim_start) / stim_period) * stim_period <= stim_duration )), 0 ); dVdt := (-(1) / Cm) * (i_Na + i_Ca_L + i_Ca_T + i_Kr + i_Ks + i_K_Na + i_K_ATP + i_to + i_K1 + i_Kp + i_NaCa + i_p_Ca + i_Na_b + i_Ca_b + i_NaK + i_ns_Ca + I_st); // Rate Rules: V' = (-(1) / Cm) * (i_Na + i_Ca_L + i_Ca_T + i_Kr + i_Ks + i_K_Na + i_K_ATP + i_to + i_K1 + i_Kp + i_NaCa + i_p_Ca + i_Na_b + i_Ca_b + i_NaK + i_ns_Ca + I_st); // Variable initializations: V = -88.68; R = 8314; T = 310; F = 96485; Cm = 0.001; time_ = ; i_Na = ; i_Ca_L = ; i_Ca_T = ; i_Kr = ; i_Ks = ; i_K_Na = ; i_K_ATP = ; i_to = ; i_NaCa = ; i_K1 = ; i_Kp = ; i_p_Ca = ; i_Na_b = ; i_Ca_b = ; i_NaK = ; i_ns_Ca = ; stim_start = 0.1; stim_end = 9; stim_period = 0.75; stim_duration = 0.002; stim_amplitude = -25.5; end model clancy_rudy_2001_version01__Na_channel_states(P_O_Na, time_, V) // Assignment Rules: alpha_11 := 3802 / (0.1027 * exp(- V / 17) + 0.2 * exp(- V / 150)); beta_11 := 191.7 * exp(- V / 20.3); alpha_12 := 3802 / (0.1027 * exp(- V / 15) + 0.23 * exp(- V / 150)); beta_12 := 200 * exp(-(V - 5) / 20.3); alpha_13 := 3802 / (0.1027 * exp(- V / 12) + 0.25 * exp(- V / 150)); beta_13 := 220 * exp(-(V - 10) / 20.3); alpha_2 := 9178 * exp(V / 29.68); beta_2 := (alpha_13 * alpha_2 * alpha_3) / (beta_13 * beta_3); alpha_3 := 0.00000037933 * exp(- V / 5.2); beta_3 := 8.4 + 0.02 * V; alpha_4 := alpha_2 / 100; beta_4 := alpha_3; // Rate Rules: P_O_Na' = -(alpha_2 + beta_13) * P_O_Na + beta_2 * P_IF + alpha_13 * P_C1; P_C1' = -(beta_12 + alpha_13 + beta_3) * P_C1 + alpha_12 * P_C2 + beta_13 * P_O_Na + alpha_3 * P_IF; P_C2' = -(beta_11 + alpha_12) * P_C2 + alpha_11 * P_C3 + beta_12 * P_C1; P_C3' = beta_11 * P_C2 - alpha_11 * P_C3; P_IF' = -(beta_2 + alpha_3 + alpha_4) * P_IF + beta_3 * P_C1 + beta_4 * P_IS + alpha_2 * P_O_Na; P_IS' = alpha_4 * P_IF - beta_4 * P_IS; // Variable initializations: P_O_Na = 5.0638e-8; P_C1 = 6.3126e-5; P_C2 = 0.01286; P_C3 = 0.987; P_IF = 4.329e-5; P_IS = 2.0725e-5; time_ = ; V = ; end model clancy_rudy_2001_version01__fast_sodium_current(i_Na, E_Na, time_, V, R, T, F, Nao, Nai, P_O_Na) // Sub-modules, and any changes to those submodules: Na_channel_states: clancy_rudy_2001_version01__Na_channel_states(P_O_Na, time_, V); // Assignment Rules: i_Na := g_Na * P_O_Na * (V - E_Na); E_Na := ((R * T) / F) * ln(Nao / Nai); // Variable initializations: g_Na = 18.5; R = ; T = ; F = ; Nao = ; Nai = ; end model clancy_rudy_2001_version01__L_type_Ca_channel_d_gate(d, V, time_) // Assignment Rules: alpha_d := d_infinity / tau_d; beta_d := (1 - d_infinity) / tau_d; d_infinity := 1 / (1 + exp(- E0_d / 6.24)); tau_d := piecewise( 0.001 / (0.035 * 6.24) , abs(E0_d) < 1E-5 , (0.001 * d_infinity * (1 - exp(- E0_d / 6.24))) / (0.035 * E0_d) ); E0_d := V + 10; // Rate Rules: d' = alpha_d * (1 - d) - beta_d * d; // Variable initializations: d = 3.34188e-6; V = ; time_ = ; end model clancy_rudy_2001_version01__L_type_Ca_channel_f_gate(f, V, time_) // Assignment Rules: alpha_f := f_infinity / tau_f; beta_f := (1 - f_infinity) / tau_f; f_infinity := 1 / (1 + exp((V + 32) / 8)) + 0.6 / (1 + exp((50 - V) / 20)); tau_f := 0.001 / (0.0197 * exp(-power(0.0337 * (V + 10), 2)) + 0.02); // Rate Rules: f' = alpha_f * (1 - f) - beta_f * f; // Variable initializations: f = 0.999747; V = ; time_ = ; end model clancy_rudy_2001_version01__L_type_Ca_channel_f_Ca_gate(f_Ca, V, time_, Cai) // Assignment Rules: f_Ca := 1 / (1 + Cai / Km_Ca); // Variable initializations: Km_Ca = 0.0006; V = ; time_ = ; Cai = ; end model clancy_rudy_2001_version01__L_type_Ca_channel(i_Ca_L, i_CaCa, i_CaK, i_CaNa, gamma_Nai, gamma_Nao, gamma_Ki, gamma_Ko, time_, V, Cai, R, T, F, Cao, Nao, Ko, Nai, Ki, d, f, f_Ca) // Sub-modules, and any changes to those submodules: L_type_Ca_channel_d_gate: clancy_rudy_2001_version01__L_type_Ca_channel_d_gate(d, V, time_); L_type_Ca_channel_f_gate: clancy_rudy_2001_version01__L_type_Ca_channel_f_gate(f, V, time_); L_type_Ca_channel_f_Ca_gate: clancy_rudy_2001_version01__L_type_Ca_channel_f_Ca_gate(f_Ca, V, time_, Cai); // Assignment Rules: i_Ca_L := i_CaCa + i_CaK + i_CaNa; i_CaCa := d * f * f_Ca * I_CaCa; i_CaK := d * f * f_Ca * I_CaK; i_CaNa := d * f * f_Ca * I_CaNa; I_CaCa := (((P_Ca * power(2, 2) * V * power(F, 2)) / (R * T)) * (gamma_Cai * Cai * exp((2 * V * F) / (R * T)) - gamma_Cao * Cao)) / (exp((2 * V * F) / (R * T)) - 1); I_CaK := (((P_K * power(1, 2) * V * power(F, 2)) / (R * T)) * (gamma_Ki * Ki * exp((1 * V * F) / (R * T)) - gamma_Ko * Ko)) / (exp((1 * V * F) / (R * T)) - 1); I_CaNa := (((P_Na * power(1, 2) * V * power(F, 2)) / (R * T)) * (gamma_Nai * Nai * exp((1 * V * F) / (R * T)) - gamma_Nao * Nao)) / (exp((1 * V * F) / (R * T)) - 1); // Variable initializations: gamma_Nai = 0.75; gamma_Nao = 0.75; gamma_Ki = 0.75; gamma_Ko = 0.75; P_Ca = 0.00054; P_Na = 6.75e-7; P_K = 1.93e-7; gamma_Cai = 1; gamma_Cao = 0.341; R = ; T = ; F = ; Cao = ; Nao = ; Ko = ; Nai = ; Ki = ; end model clancy_rudy_2001_version01__T_type_Ca_channel_b_gate(b, V, time_) // Assignment Rules: b_inf := 1 / (1 + exp(-(V + 14) / 10.8)); tau_b := 0.0037 + 0.0061 / (1 + exp((V + 25) / 4.5)); // Rate Rules: b' = (b_inf - b) / tau_b; // Variable initializations: b = 0.000992; V = ; time_ = ; end model clancy_rudy_2001_version01__T_type_Ca_channel_g_gate(g, V, time_) // Assignment Rules: g_inf := 1 / (1 + exp((V + 60) / 5.6)); tau_g := piecewise( -(0.000875) * V + 0.012 , V <= 0 , 0.012 ); // Rate Rules: g' = (g_inf - g) / tau_g; // Variable initializations: g = 0.99407; V = ; time_ = ; end model clancy_rudy_2001_version01__T_type_Ca_channel(i_Ca_T, E_Ca, time_, V, b, g) // Sub-modules, and any changes to those submodules: T_type_Ca_channel_b_gate: clancy_rudy_2001_version01__T_type_Ca_channel_b_gate(b, V, time_); T_type_Ca_channel_g_gate: clancy_rudy_2001_version01__T_type_Ca_channel_g_gate(g, V, time_); // Assignment Rules: i_Ca_T := g_CaT * b * b * g * (V - E_Ca); // Variable initializations: g_CaT = 0.05; E_Ca = ; end model clancy_rudy_2001_version01__Kr_channel_states(P_O, time_, V, Ko) // Assignment Rules: alpha := 55.5 * exp(0.05547153 * (V + 6)); beta := 2.357 * exp(-(0.036588) * V); alpha_alpha := 65.5 * exp(0.05547153 * (V + 25)); beta_beta := 2.9357 * exp(-(0.02158) * V); alpha_i := (439 * exp(-(0.02352) * (V + 25)) * 4.5) / Ko; beta_i := 656 * exp(0.000942 * V) * power(4.5 / Ko, 0.3); mu := (alpha_i * beta_beta * alpha_alpha) / (alpha_alpha * beta_i); // Rate Rules: P_O' = -(beta_beta + beta_i) * P_O + alpha_alpha * P_C1 + alpha_i * P_I; P_C1' = -(beta_in + alpha_alpha + alpha_alpha) * P_C1 + alpha_in * P_C2 + beta_beta * P_O + mu * P_I; P_C2' = -(beta + alpha_in) * P_C2 + alpha * P_C3 + beta_in * P_C1; P_C3' = beta * P_C2 - alpha * P_C3; P_I' = -(mu + alpha_i) * P_I + alpha_alpha * P_C1 + beta_i * P_O; // Variable initializations: P_O = 8.8075e-9; P_C1 = 9.15215e-8; P_C2 = 4.5382e-8; P_C3 = 4.8516e-6; P_I = 2.7074e-9; alpha_in = 2172; beta_in = 1077; time_ = ; V = ; Ko = ; end model clancy_rudy_2001_version01__rapid_delayed_rectifier_potassium_current(i_Kr, time_, V, Ko, Ki, R, T, F, P_O) // Sub-modules, and any changes to those submodules: Kr_channel_states: clancy_rudy_2001_version01__Kr_channel_states(P_O, time_, V, Ko); // Assignment Rules: i_Kr := g_Kr * P_O * (V - E_Kr); g_Kr := 2.7 * 0.0135 * power(Ko, 0.59); E_Kr := ((R * T) / F) * ln(Ko / Ki); // Variable initializations: Ki = ; R = ; T = ; F = ; end model clancy_rudy_2001_version01__slow_delayed_rectifier_potassium_current_xs1_gate(xs1, V, time_) // Assignment Rules: xs1_infinity := 1 / (1 + exp(-(V - 1.5) / 16.7)); tau_xs1 := 0.001 / ((7.19E-5 * (V + 30)) / (1 - exp(-(0.148) * (V + 30))) + (0.000131 * (V + 30)) / (exp(0.0687 * (V + 30)) - 1)); // Rate Rules: xs1' = (xs1_infinity - xs1) / tau_xs1; // Variable initializations: xs1 = 0.004497; V = ; time_ = ; end model clancy_rudy_2001_version01__slow_delayed_rectifier_potassium_current_xs2_gate(xs2, V, time_) // Assignment Rules: xs2_infinity := 1 / (1 + exp(-(V - 1.5) / 16.7)); tau_xs2 := (4 * 0.001) / ((7.19E-5 * (V + 30)) / (1 - exp(-(0.148) * (V + 30))) + (0.000131 * (V + 30)) / (exp(0.0687 * (V + 30)) - 1)); // Rate Rules: xs2' = (xs2_infinity - xs2) / tau_xs2; // Variable initializations: xs2 = 0.00445979; V = ; time_ = ; end model clancy_rudy_2001_version01__slow_delayed_rectifier_potassium_current(i_Ks, time_, V, R, T, F, Ko, Ki, Nao, Nai, Cai, xs1, xs2) // Sub-modules, and any changes to those submodules: slow_delayed_rectifier_potassium_current_xs1_gate: clancy_rudy_2001_version01__slow_delayed_rectifier_potassium_current_xs1_gate(xs1, V, time_); slow_delayed_rectifier_potassium_current_xs2_gate: clancy_rudy_2001_version01__slow_delayed_rectifier_potassium_current_xs2_gate(xs2, V, time_); // Assignment Rules: i_Ks := g_Ks * xs1 * xs2 * (V - E_Ks); g_Ks := 0.433 * (1 + 0.6 / (1 + power(3.8E-5 / Cai, 1.4))); E_Ks := ((R * T) / F) * ln((Ko + PNaK * Nao) / (Ki + PNaK * Nai)); // Variable initializations: PNaK = 0.01833; R = ; T = ; F = ; Ko = ; Ki = ; Nao = ; Nai = ; Cai = ; end model clancy_rudy_2001_version01__time_independent_potassium_current_K1_gate(K1_infinity, V, time_, E_K) // Assignment Rules: K1_infinity := alpha_K1 / (alpha_K1 + beta_K1); alpha_K1 := 1020 / (1 + exp(0.2385 * ((V - E_K) - 59.215))); beta_K1 := (1000 * (0.49124 * exp(0.08032 * ((V - E_K) + 5.476)) + exp(0.06175 * ((V - E_K) - 594.31)))) / (1 + exp(-(0.5143) * ((V - E_K) + 4.753))); // Variable initializations: V = ; time_ = ; E_K = ; end model clancy_rudy_2001_version01__time_independent_potassium_current(i_K1, E_K, time_, V, Ko, Ki, R, T, F, K1_infinity) // Sub-modules, and any changes to those submodules: time_independent_potassium_current_K1_gate: clancy_rudy_2001_version01__time_independent_potassium_current_K1_gate(K1_infinity, V, time_, E_K); // Assignment Rules: i_K1 := g_K1 * K1_infinity * (V - E_K); E_K := ((R * T) / F) * ln(Ko / Ki); g_K1 := 0.75 * root(Ko / 5.4); // Variable initializations: Ko = ; Ki = ; R = ; T = ; F = ; end model clancy_rudy_2001_version01__plateau_potassium_current(i_Kp, time_, V, E_K) // Assignment Rules: i_Kp := g_Kp * Kp * (V - E_K); Kp := 1 / (1 + exp((7.488 - V) / 5.98)); // Variable initializations: g_Kp = 0.00552; time_ = ; V = ; E_K = ; end model clancy_rudy_2001_version01__sodium_activated_potassium_current(i_K_Na, time_, V, Nai, E_K) // Assignment Rules: i_K_Na := g_K_Na * pona * pov * (V - E_K); g_K_Na := 0 * 0.12848; pona := 0.85 / (1 + power(kdKNa / Nai, nKNa)); pov := 0.8 - 0.65 / (1 + exp((V + 125) / 15)); // Variable initializations: nKNa = 2.8; kdKNa = 66; time_ = ; V = ; Nai = ; E_K = ; end model clancy_rudy_2001_version01__ATP_sensitive_potassium_current(i_K_ATP, time_, V, Ko, E_K) // Assignment Rules: i_K_ATP := GKbaraATP * (V - E_K); g_K_ATP := (i_K_ATP_on * 0.000193) / nicholsarea; pATP := 1 / (1 + power(ATPi / kATP, hATP)); GKbaraATP := g_K_ATP * pATP * power(Ko / 4, nATP); // Variable initializations: i_K_ATP_on = 1; nATP = 0.24; nicholsarea = 5e-5; ATPi = 3; hATP = 2; kATP = 0.00025; time_ = ; V = ; Ko = ; E_K = ; end model clancy_rudy_2001_version01__transient_outward_current_zdv_gate(zdv, V, time_) // Assignment Rules: alpha_zdv := (10000 * exp((V - 40) / 25)) / (1 + exp((V - 40) / 25)); beta_zdv := (10000 * exp(-(V + 90) / 25)) / (1 + exp(-(V + 90) / 25)); tau_zdv := 1 / (alpha_zdv + beta_zdv); zdv_ss := alpha_zdv / (alpha_zdv + beta_zdv); // Rate Rules: zdv' = (zdv_ss - zdv) / tau_zdv; // Variable initializations: zdv = 0.011738; V = ; time_ = ; end model clancy_rudy_2001_version01__transient_outward_current_ydv_gate(ydv, V, time_) // Assignment Rules: alpha_ydv := 15 / (1 + exp((V + 60) / 5)); beta_ydv := (100 * exp((V + 25) / 5)) / (1 + exp((V + 25) / 5)); tau_ydv := 1 / (alpha_ydv + beta_ydv); ydv_ss := alpha_ydv / (alpha_ydv + beta_ydv); // Rate Rules: ydv' = (ydv_ss - ydv) / tau_ydv; // Variable initializations: ydv = 0.99998; V = ; time_ = ; end model clancy_rudy_2001_version01__transient_outward_current(i_to, E_K, V, time_, zdv, ydv) // Sub-modules, and any changes to those submodules: transient_outward_current_zdv_gate: clancy_rudy_2001_version01__transient_outward_current_zdv_gate(zdv, V, time_); transient_outward_current_ydv_gate: clancy_rudy_2001_version01__transient_outward_current_ydv_gate(ydv, V, time_); // Assignment Rules: i_to := g_to * power(zdv, 3) * ydv * rvdv * (V - E_K); g_to := 0 * 0.5; rvdv := exp(V / 100); // Variable initializations: E_K = ; end model clancy_rudy_2001_version01__sarcolemmal_calcium_pump(i_p_Ca, time_, Cai) // Assignment Rules: i_p_Ca := (I_pCa * Cai) / (K_mpCa + Cai); // Variable initializations: K_mpCa = 0.0005; I_pCa = 1.15; time_ = ; Cai = ; end model clancy_rudy_2001_version01__sodium_background_current(i_Na_b, time_, V, E_Na) // Assignment Rules: i_Na_b := g_Nab * (V - E_Na); // Variable initializations: g_Nab = 0.004; time_ = ; V = ; E_Na = ; end model clancy_rudy_2001_version01__calcium_background_current(i_Ca_b, E_Ca, time_, V, R, T, F, Cai, Cao) // Assignment Rules: i_Ca_b := g_Cab * (V - E_Ca); E_Ca := ((R * T) / (2 * F)) * ln(Cao / Cai); // Variable initializations: g_Cab = 0.003016; time_ = ; V = ; R = ; T = ; F = ; Cai = ; Cao = ; end model clancy_rudy_2001_version01__sodium_potassium_pump(i_NaK, time_, V, R, T, F, Nai, Nao, Ko) // Assignment Rules: i_NaK := (((I_NaK * f_NaK * 1) / (1 + power(K_mNai / Nai, 2))) * Ko) / (Ko + K_mKo); f_NaK := 1 / (1 + 0.1245 * exp((-(0.1) * V * F) / (R * T)) + 0.0365 * sigma * exp((- V * F) / (R * T))); sigma := (1 / 7) * (exp(Nao / 67.3) - 1); // Variable initializations: I_NaK = 2.25; K_mNai = 10; K_mKo = 1.5; time_ = ; V = ; R = ; T = ; F = ; Nai = ; Nao = ; Ko = ; end model clancy_rudy_2001_version01__non_specific_calcium_activated_current(i_ns_Ca, i_ns_Na, i_ns_K, gamma_Nai, gamma_Nao, gamma_Ki, gamma_Ko, R, T, F, Cao, Nao, Ko, Nai, Ki, time_, Cai, V) // Assignment Rules: i_ns_Ca := i_ns_Na + i_ns_K; i_ns_Na := (I_ns_Na * 1) / (1 + power(K_m_ns_Ca / Cai, 3)); i_ns_K := (I_ns_K * 1) / (1 + power(K_m_ns_Ca / Cai, 3)); P_ns_Ca := 0 * 1.75E-7; I_ns_Na := (((P_ns_Ca * power(1, 2) * V * power(F, 2)) / (R * T)) * (gamma_Nai * Nai * exp((1 * V * F) / (R * T)) - gamma_Nao * Nao)) / (exp((1 * V * F) / (R * T)) - 1); I_ns_K := (((P_ns_Ca * power(1, 2) * V * power(F, 2)) / (R * T)) * (gamma_Ki * Ki * exp((1 * V * F) / (R * T)) - gamma_Ko * Ko)) / (exp((1 * V * F) / (R * T)) - 1); // Variable initializations: gamma_Nai = ; gamma_Nao = ; gamma_Ki = ; gamma_Ko = ; R = ; T = ; F = ; Cao = ; Nao = ; Ko = ; Nai = ; Ki = ; K_m_ns_Ca = 0.0012; time_ = ; Cai = ; V = ; end model clancy_rudy_2001_version01__Na_Ca_exchanger(i_NaCa, time_, V, R, T, F, Nai, Nao, Cai, Cao) // Assignment Rules: i_NaCa := (c1 * exp(((gamma - 1) * V * F) / (R * T)) * (exp((V * F) / (R * T)) * power(Nai, 3) * Cao - power(Nao, 3) * Cai)) / (1 + c2 * exp(((gamma - 1) * V * F) / (R * T)) * (exp((V * F) / (R * T)) * power(Nai, 3) * Cao + power(Nao, 3) * Cai)); // Variable initializations: c1 = 0.00025; c2 = 0.0001; gamma = 0.15; time_ = ; V = ; R = ; T = ; F = ; Nai = ; Nao = ; Cai = ; Cao = ; end model clancy_rudy_2001_version01__calcium_dynamics(i_rel, i_up, i_leak, i_tr, time_, F, Cai, Cao, Ca_JSR, Ca_NSR, V_myo, A_cap, i_NaCa, i_CaCa, i_p_Ca, i_Ca_b, i_Ca_T, dVdt) // Assignment Rules: i_rel := G_rel * (Ca_JSR - Cai); i_up := (I_up * Cai) / (Cai + K_mup); i_leak := K_leak * Ca_NSR; i_tr := (Ca_NSR - Ca_JSR) / tau_tr; G_rel := piecewise( ((G_rel_max * (Cainfluxtrack - delta_Ca_ith)) / ((K_mrel + Cainfluxtrack) - delta_Ca_ith)) * (1 - APtrack2) * APtrack2 , Cainfluxtrack > delta_Ca_ith , G_rel_overload * (1 - OVRLDtrack2) * OVRLDtrack2 , ( Cainfluxtrack <= delta_Ca_ith) && (OVRLDtrack2 > 0 ), 0 ); K_leak := I_up / Ca_NSR_max; V_JSR := (0.0048 / 0.68) * V_myo; V_NSR := (0.0552 / 0.68) * V_myo; // Rate Rules: Cai' = (1 / (1 + (CMDN_max * K_mCMDN) / power(K_mCMDN + Cai, 2) + (Tn_max * K_mTn) / power(K_mTn + Cai, 2))) * ((- A_cap * (((i_CaCa + i_Ca_T) - 2 * i_NaCa) + i_p_Ca + i_Ca_b)) / (2 * V_myo * F) + (i_rel * V_JSR) / V_myo + ((i_leak - i_up) * V_NSR) / V_myo); Ca_JSR' = (1 / (1 + (CSQN_max * K_mCSQN) / power(K_mCSQN + Ca_JSR, 2))) * (i_tr - i_rel); Ca_NSR' = ((- i_tr * V_JSR) / V_NSR - i_leak) + i_up; APtrack' = piecewise( 100000 * (1 - APtrack) - 500 * APtrack , dVdt > 150000 , -(500) * APtrack ); APtrack2' = piecewise( 100000 * (1 - APtrack2) - 500 * APtrack2 , ( APtrack < 0.2) && (APtrack > 0.18 ), -(500) * APtrack2 ); APtrack3' = piecewise( 100000 * (1 - APtrack3) - 500 * APtrack3 , ( APtrack < 0.2) && (APtrack > 0.18 ), -(10) * APtrack3 ); Cainfluxtrack' = piecewise( (- A_cap * (((i_CaCa + i_Ca_T) - i_NaCa) + i_p_Ca + i_Ca_b)) / (2 * V_myo * F) , APtrack > 0.2 , 0 , ( APtrack2 > 0.01) && (APtrack <= 0.2 ), -(500) * Cainfluxtrack ); OVRLDtrack' = piecewise( 50000 * (1 - OVRLDtrack) , (( 1 / (1 + K_mCSQN / Ca_NSR) > CSQNthresh) && (OVRLDtrack3 < 0.37) && (APtrack3 < 0.37 )), -(500) * OVRLDtrack ); OVRLDtrack2' = piecewise( 50000 * (1 - OVRLDtrack2) , ( OVRLDtrack > Logicthresh) && (OVRLDtrack2 < Logicthresh ), -(500) * OVRLDtrack2 ); OVRLDtrack3' = piecewise( 50000 * (1 - OVRLDtrack3) , ( OVRLDtrack > Logicthresh) && (OVRLDtrack3 < Logicthresh ), -(10) * OVRLDtrack3 ); // Variable initializations: G_rel_max = 60000; G_rel_overload = 4000; tau_tr = 0.18; K_mrel = 0.0008; delta_Ca_ith = 0.00018; CSQN_max = 10; K_mCSQN = 0.8; K_mup = 0.00092; I_up = 8.75; Ca_NSR_max = 15; time_ = ; F = ; Cai = 0.00010186; Cao = 1.8; Ca_JSR = 1.494; Ca_NSR = 1.494; V_myo = ; A_cap = ; i_NaCa = ; i_CaCa = ; i_p_Ca = ; i_Ca_b = ; i_Ca_T = ; K_mTn = 0.0005; K_mCMDN = 0.00238; Tn_max = 0.07; CMDN_max = 0.05; dVdt = ; APtrack = 0; APtrack2 = 0; APtrack3 = 0; Cainfluxtrack = 0; OVRLDtrack = 0; OVRLDtrack2 = 0; OVRLDtrack3 = 0; CSQNthresh = 0.7; Logicthresh = 0.98; end model clancy_rudy_2001_version01__ionic_concentrations(Nai, Nao, Ki, Ko, A_cap, V_myo, time_, F, i_Na, i_CaNa, i_Na_b, i_ns_Na, i_NaCa, i_NaK, i_CaK, i_Kr, i_Ks, i_K1, i_Kp, i_K_Na, i_K_ATP, i_ns_K, i_to) // Assignment Rules: V_myo := 0.68 * volume; // Rate Rules: Nai' = (-(i_Na + i_CaNa + i_Na_b + i_ns_Na + i_NaCa * 3 + i_NaK * 3) * A_cap) / (V_myo * F); Ki' = (-(i_CaK + i_Kr + i_Ks + i_K1 + i_Kp + i_K_Na + i_K_ATP + i_to + i_ns_K + - i_NaK * 2) * A_cap) / (V_myo * F); // Variable initializations: Nai = 10.1134; Nao = 132; Ki = 140.718; Ko = 4.5; A_cap = 1.434e-7; preplength = 0.001; radius = 1.1e-4; time_ = ; F = ; i_Na = ; i_CaNa = ; i_Na_b = ; i_ns_Na = ; i_NaCa = ; i_NaK = ; i_CaK = ; i_Kr = ; i_Ks = ; i_K1 = ; i_Kp = ; i_K_Na = ; i_K_ATP = ; i_ns_K = ; i_to = ; // Unit definitions: unit volume = litre; end model *clancy_rudy_2001_version01____main() // Sub-modules, and any changes to those submodules: environment: clancy_rudy_2001_version01__environment(time_); membrane: clancy_rudy_2001_version01__membrane(V, R, T, F, time_, i_Na, i_Ca_L, i_Ca_T, i_Kr, i_Ks, i_K_Na, i_K_ATP, i_to, i_NaCa, i_K1, i_Kp, i_p_Ca, i_Na_b, i_Ca_b, i_NaK, i_ns_Ca, dVdt); fast_sodium_current: clancy_rudy_2001_version01__fast_sodium_current(i_Na, E_Na, time_, V, R, T, F, Nao, Nai, P_O_Na); L_type_Ca_channel: clancy_rudy_2001_version01__L_type_Ca_channel(i_Ca_L, i_CaCa, i_CaK, i_CaNa, gamma_Nai, gamma_Nao, gamma_Ki, gamma_Ko, time_, V, Cai, R, T, F, Cao, Nao, Ko, Nai, Ki, d, f, f_Ca); T_type_Ca_channel: clancy_rudy_2001_version01__T_type_Ca_channel(i_Ca_T, E_Ca, time_, V, b, g); rapid_delayed_rectifier_potassium_current: clancy_rudy_2001_version01__rapid_delayed_rectifier_potassium_current(i_Kr, time_, V, Ko, Ki, R, T, F, P_O); slow_delayed_rectifier_potassium_current: clancy_rudy_2001_version01__slow_delayed_rectifier_potassium_current(i_Ks, time_, V, R, T, F, Ko, Ki, Nao, Nai, Cai, xs1, xs2); time_independent_potassium_current: clancy_rudy_2001_version01__time_independent_potassium_current(i_K1, E_K, time_, V, Ko, Ki, R, T, F, K1_infinity); plateau_potassium_current: clancy_rudy_2001_version01__plateau_potassium_current(i_Kp, time_, V, E_K); sodium_activated_potassium_current: clancy_rudy_2001_version01__sodium_activated_potassium_current(i_K_Na, time_, V, Nai, E_K); ATP_sensitive_potassium_current: clancy_rudy_2001_version01__ATP_sensitive_potassium_current(i_K_ATP, time_, V, Ko, E_K); transient_outward_current: clancy_rudy_2001_version01__transient_outward_current(i_to, E_K, V, time_, zdv, ydv); sarcolemmal_calcium_pump: clancy_rudy_2001_version01__sarcolemmal_calcium_pump(i_p_Ca, time_, Cai); sodium_background_current: clancy_rudy_2001_version01__sodium_background_current(i_Na_b, time_, V, E_Na); calcium_background_current: clancy_rudy_2001_version01__calcium_background_current(i_Ca_b, E_Ca, time_, V, R, T, F, Cai, Cao); sodium_potassium_pump: clancy_rudy_2001_version01__sodium_potassium_pump(i_NaK, time_, V, R, T, F, Nai, Nao, Ko); non_specific_calcium_activated_current: clancy_rudy_2001_version01__non_specific_calcium_activated_current(i_ns_Ca, i_ns_Na, i_ns_K, gamma_Nai, gamma_Nao, gamma_Ki, gamma_Ko, R, T, F, Cao, Nao, Ko, Nai, Ki, time_, Cai, V); Na_Ca_exchanger: clancy_rudy_2001_version01__Na_Ca_exchanger(i_NaCa, time_, V, R, T, F, Nai, Nao, Cai, Cao); calcium_dynamics: clancy_rudy_2001_version01__calcium_dynamics(i_rel, i_up, i_leak, i_tr, time_, F, Cai, Cao, Ca_JSR, Ca_NSR, V_myo, A_cap, i_NaCa, i_CaCa, i_p_Ca, i_Ca_b, i_Ca_T, dVdt); ionic_concentrations: clancy_rudy_2001_version01__ionic_concentrations(Nai, Nao, Ki, Ko, A_cap, V_myo, time_, F, i_Na, i_CaNa, i_Na_b, i_ns_Na, i_NaCa, i_NaK, i_CaK, i_Kr, i_Ks, i_K1, i_Kp, i_K_Na, i_K_ATP, i_ns_K, i_to); end