//Created by libAntimony v2.4 model Niederer_et_al_2006__environment(time_) // Variable initializations: time_ = ; end model Niederer_et_al_2006__intracellular_ion_concentrations(time_, Ca_i, Ca_b, TRPN, Ca_TRPN_Max, J_TRPN) // Assignment Rules: Ca_i := piecewise( 1000 * 1.8433E-7 , time_ < 1 , 1000 * (((1.055 * power(time_ / 1000, 3) - 0.03507 * power(time_ / 1000, 2)) + (0.0003992 * time_) / 1000) - 1.356E-6) , ( geq(time_, 10)) && (time_ < 15 ), 1000 * (((0.014 * power(time_ / 1000, 3) - 0.002555 * power(time_ / 1000, 2)) + (0.0001494 * time_) / 1000) - 1.428E-6) , ( geq(time_, 15)) && (time_ < 55 ), 1000 * (((1.739E-5 * power(time_ / 1000, 3) - 3.209E-6 * power(time_ / 1000, 2)) - (5.689E-6 * time_) / 1000) + 1.719E-6) , ( geq(time_, 55)) && (time_ < 250 ), 1000 * ((((0.0001321 * power(time_ / 1000, 4) - 0.0002197 * power(time_ / 1000, 3)) + 0.0001374 * power(time_ / 1000, 2)) - (3.895E-5 * time_) / 1000) + 4.441E-6) , ( geq(time_, 250)) && (time_ < 490 ), 1000 * 1.2148E-7 ); Ca_b := Ca_TRPN_Max - TRPN; // Rate Rules: TRPN' = J_TRPN; // Variable initializations: time_ = ; TRPN = 0.067593139865; Ca_TRPN_Max = ; J_TRPN = ; end model Niederer_et_al_2006__thinfilaments() end model Niederer_et_al_2006__tropomyosin(z, z_max, time_, k_on, k_Ref_off, gamma_trpn, Ca_TRPN_Max, beta_0, Ca_b, lambda) // Assignment Rules: z_max := (alpha_0 / power(Ca_TRPN_50 / Ca_TRPN_Max, n_Hill) - K_2) / (alpha_r1 + K_1 + alpha_0 / power(Ca_TRPN_50 / Ca_TRPN_Max, n_Hill)); Ca_50 := Ca_50ref * (1 + beta_1 * (lambda - 1)); Ca_TRPN_50 := (Ca_50 * Ca_TRPN_Max) / (Ca_50 + (k_Ref_off / k_on) * (1 - ((1 + beta_0 * (lambda - 1)) * 0.5) / gamma_trpn)); K_2 := ((alpha_r2 * power(z_p, n_Rel)) / (power(z_p, n_Rel) + power(K_z, n_Rel))) * (1 - (n_Rel * power(K_z, n_Rel)) / (power(z_p, n_Rel) + power(K_z, n_Rel))); K_1 := (alpha_r2 * power(z_p, n_Rel - 1) * n_Rel * power(K_z, n_Rel)) / power(power(z_p, n_Rel) + power(K_z, n_Rel), 2); alpha_Tm := alpha_0 * power(Ca_b / Ca_TRPN_50, n_Hill); beta_Tm := alpha_r1 + (alpha_r2 * power(z, n_Rel - 1)) / (power(z, n_Rel) + power(K_z, n_Rel)); // Rate Rules: z' = alpha_Tm * (1 - z) - beta_Tm * z; // Variable initializations: z = 0.014417937837; time_ = ; k_on = ; k_Ref_off = ; gamma_trpn = ; Ca_TRPN_Max = ; alpha_0 = 8e-3; alpha_r1 = 2e-3; alpha_r2 = 1.75e-3; n_Rel = 3; K_z = 0.15; n_Hill = 3; Ca_50ref = 1.05e-3; z_p = 0.85; beta_1 = -4; beta_0 = ; Ca_b = ; lambda = ; end model Niederer_et_al_2006__troponin(J_TRPN, Ca_TRPN_Max, TRPN, Ca_i, k_on, k_Ref_off, gamma_trpn, Tension, T_ref) // Assignment Rules: J_TRPN := (Ca_TRPN_Max - TRPN) * k_off - Ca_i * TRPN * k_on; k_off := piecewise( k_Ref_off * (1 - Tension / (gamma_trpn * T_ref)) , 1 - Tension / (gamma_trpn * T_ref) > 0.1 , k_Ref_off * 0.1 ); // Variable initializations: Ca_TRPN_Max = 70e-3; TRPN = ; Ca_i = ; k_on = 100; k_Ref_off = 0.2; gamma_trpn = 2; Tension = ; T_ref = ; end model Niederer_et_al_2006__Myofilaments(time_, lambda, ExtensionRatio, dExtensionRatiodt, lambda_prev) // Assignment Rules: lambda := piecewise( ExtensionRatio , ( ExtensionRatio > 0.8) && (ExtensionRatio <= 1.15 ), 1.15 , ExtensionRatio > 1.15 , 0.8 ); ExtensionRatio := piecewise( 1 , time_ > 3E5 , 1 ); dExtensionRatiodt := 0; lambda_prev := ExtensionRatio; // Variable initializations: time_ = ; end model Niederer_et_al_2006__filament_overlap(lambda, overlap, beta_0) // Assignment Rules: overlap := 1 + beta_0 * (lambda - 1); // Variable initializations: lambda = ; beta_0 = 4.9; end model Niederer_et_al_2006__length_independent_tension(T_ref, T_Base, z, z_max) // Assignment Rules: T_Base := (T_ref * z) / z_max; // Variable initializations: T_ref = 56.2; z = ; z_max = ; end model Niederer_et_al_2006__isometric_tension(T_0, T_Base, overlap) // Assignment Rules: T_0 := T_Base * overlap; // Variable initializations: T_Base = ; overlap = ; end model Niederer_et_al_2006__Cross_Bridges(time_, dExtensionRatiodt, T_0, Tension) // Assignment Rules: Q := Q_1 + Q_2 + Q_3; Tension := piecewise( (T_0 * (a * Q + 1)) / (1 - Q) , Q < 0 , (T_0 * (1 + (a + 2) * Q)) / (1 + Q) ); // Rate Rules: Q_1' = A_1 * dExtensionRatiodt - alpha_1 * Q_1; Q_2' = A_2 * dExtensionRatiodt - alpha_2 * Q_2; Q_3' = A_3 * dExtensionRatiodt - alpha_3 * Q_3; // Variable initializations: time_ = ; dExtensionRatiodt = ; a = 0.35; Q_1 = 0; Q_2 = 0; Q_3 = 0; A_1 = -29; A_2 = 138; A_3 = 129; alpha_1 = 0.03; alpha_2 = 0.13; alpha_3 = 0.625; T_0 = ; end model *Niederer_et_al_2006____main() // Sub-modules, and any changes to those submodules: environment: Niederer_et_al_2006__environment(time_); intracellular_ion_concentrations: Niederer_et_al_2006__intracellular_ion_concentrations(time_, Ca_i, Ca_b, TRPN, Ca_TRPN_Max, J_TRPN); thinfilaments: Niederer_et_al_2006__thinfilaments(); tropomyosin: Niederer_et_al_2006__tropomyosin(z, z_max, time_, k_on, k_Ref_off, gamma_trpn, Ca_TRPN_Max, beta_0, Ca_b, lambda); troponin: Niederer_et_al_2006__troponin(J_TRPN, Ca_TRPN_Max, TRPN, Ca_i, k_on, k_Ref_off, gamma_trpn, Tension, T_ref); Myofilaments: Niederer_et_al_2006__Myofilaments(time_, lambda, ExtensionRatio, dExtensionRatiodt, lambda_prev); filament_overlap: Niederer_et_al_2006__filament_overlap(lambda, overlap, beta_0); length_independent_tension: Niederer_et_al_2006__length_independent_tension(T_ref, T_Base, z, z_max); isometric_tension: Niederer_et_al_2006__isometric_tension(T_0, T_Base, overlap); Cross_Bridges: Niederer_et_al_2006__Cross_Bridges(time_, dExtensionRatiodt, T_0, Tension); end