//Created by libAntimony v2.4 // Warnings from automatic translation: // Unable to use the formula "CaBu * k2b - Cai * Bu * k1b" to set the assignment rule for Cai: Loop detected: Cai's definition (CaBu * k2b - Cai * Bu * k1b) 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 "CaBu * k2b - Cai * Bu * k1b" to set the assignment rule for Bu: Loop detected: Bu's definition (CaBu * k2b - Cai * Bu * k1b) 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 "Cai * Bu * k1b - CaBu * k2b" to set the assignment rule for CaBu: Loop detected: CaBu's definition (Cai * Bu * k1b - CaBu * k2b) 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 "A * k1f - (B * k1b + B * k2)" to set the assignment rule for B: Loop detected: B's definition (A * k1f - (B * k1b + B * k2)) 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 "Dyi2 * kbd - Dy * kfd" to set the assignment rule for Dy: Loop detected: Dy's definition (Dyi2 * kbd - Dy * kfd) 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 "Dy * Cai * k1d - CaDy * k2d" to set the assignment rule for CaDy: Loop detected: CaDy's definition (Dy * Cai * k1d - CaDy * k2d) either includes itself directly (i.e. 's5 := 6 + s5') or by proxy (i.e. 's5 := 8*d3' and 'd3 := 9*s5'). model warashina_2004__environment(time_) // Variable initializations: time_ = ; end model warashina_2004__membrane(V, time_, i_Na, i_sp, i_K, i_l, i_Ca, i_SK, i_ex) // Rate Rules: V' = -(i_sp + i_Na + i_K + i_l + i_Ca + i_SK + i_ex) / Cm; // Variable initializations: V = -75.0; Cm = 1.0; time_ = ; i_Na = ; i_sp = ; i_K = ; i_l = ; i_Ca = ; i_SK = ; i_ex = ; end model warashina_2004__excitatory_synapse(i_sp, V, time_) // Assignment Rules: i_sp := G * (V - E_rev); // Rate Rules: G' = L * (1 / tau1) - D * (1 / tau2); // Variable initializations: G = 0.001; L = 0.016; D = 0.000; E_rev = -7.0; tau1 = 1.0; tau2 = 6.3; V = ; time_ = ; end model warashina_2004__sodium_channel_m_gate(m, V, time_) // Assignment Rules: alpha_m := (0.109 * (V + 38.0)) / (1.0 - exp(-(V + 38.0) / 5.0)); beta_m := (0.0744 * (V + 38.0)) / (exp((V + 38.0) / 5.0) - 1.0); // Rate Rules: m' = alpha_m * (1.0 - m) - beta_m * m; // Variable initializations: m = 0.001; V = ; time_ = ; end model warashina_2004__sodium_channel_h_gate(h, V, time_) // Assignment Rules: alpha_h := 0.0192 * exp(-(55.0 + V) / 15.0); beta_h := 2.48 / (1.0 + exp((17.0 - V) / 21.0)); // Rate Rules: h' = alpha_h * (1.0 - h) - beta_h * h; // Variable initializations: h = 0.001; V = ; time_ = ; end model warashina_2004__sodium_channel(i_Na, time_, V, m, h) // Sub-modules, and any changes to those submodules: sodium_channel_m_gate: warashina_2004__sodium_channel_m_gate(m, V, time_); sodium_channel_h_gate: warashina_2004__sodium_channel_h_gate(h, V, time_); // Assignment Rules: i_Na := g_Na * power(m, 3.0) * h * (V - E_Na); // Variable initializations: g_Na = 40.0; E_Na = 50.0; end model warashina_2004__potassium_channel_n_gate(n, V, time_) // Assignment Rules: alpha_n := (0.012 * (V + 45.0)) / (1.0 - exp(-(45.0 + V) / 5.0)); beta_n := 0.204 * exp(-(V + 50.0) / 40.0); // Rate Rules: n' = alpha_n * (1.0 - n) - beta_n * n; // Variable initializations: n = 0.001; V = ; time_ = ; end model warashina_2004__potassium_channel(i_K, time_, V, E_K, n) // Sub-modules, and any changes to those submodules: potassium_channel_n_gate: warashina_2004__potassium_channel_n_gate(n, V, time_); // Assignment Rules: i_K := g_K * power(n, 4.0) * (V - E_K); // Variable initializations: g_K = 1.2; E_K = ; end model warashina_2004__leak_channel(i_l, V) // Assignment Rules: i_l := g_l * (V - E_l); // Variable initializations: g_l = 1.6; E_l = -65.0; V = ; end model warashina_2004__calcium_channel_m_gate(m, V, time_) // Assignment Rules: alpha_m := 5.0 / (1.0 + exp(-0.075 * (V - 5.0))); beta_m := (0.05 * (2.0 - V)) / (1.0 - exp((V - 2.0) / 8.0)); // Rate Rules: m' = alpha_m * (1.0 - m) - beta_m * m; // Variable initializations: m = 0.001; V = ; time_ = ; end model warashina_2004__calcium_channel_h_gate(h, time_) // Assignment Rules: h := Ff * exp(- time_ / tau_f) + Fm * exp(- time_ / tau_m) + Fs * exp(- time_ / tau_s) + Fr; // Variable initializations: Fr = 0.000; Ff = 0.79; Fm = 0.0; Fs = 0.0; tau_f = 500.0; tau_m = 0.000; tau_s = 0.000; time_ = ; end model warashina_2004__calcium_channel(i_Ca, time_, V, Ca0, R, T, F, m, h) // Sub-modules, and any changes to those submodules: calcium_channel_m_gate: warashina_2004__calcium_channel_m_gate(m, V, time_); calcium_channel_h_gate: warashina_2004__calcium_channel_h_gate(h, time_); // Assignment Rules: i_Ca := PCa * power(m, 2.0) * h * ghk; ghk := ((V * power(2.0 * F, 2.0)) / (R * T)) * ((Cao - Ca0 * exp((2.0 * V * F) / (R * T))) / (1.0 - exp((2.0 * V * F) / (R * T)))); // Variable initializations: PCa = 2.0; Cao = 2.0; Ca0 = ; R = ; T = ; F = ; end model warashina_2004__calcium_dependent_potassium_channel_m_gate(m, Ca0, time_) // Assignment Rules: m_infinity := Car / (1.0 + Car); tau_m := 1.0 / (beta_k * (1.0 + Car)); Car := power(Ca0 / Cac, n_SK); // Rate Rules: m' = -(m - m_infinity) / tau_m; // Variable initializations: m = 0.001; beta_k = 0.1; n_SK = 1.7; Cac = 700.0; Ca0 = ; time_ = ; end model warashina_2004__calcium_dependent_potassium_channel(i_SK, time_, V, Ca0, E_K, m) // Sub-modules, and any changes to those submodules: calcium_dependent_potassium_channel_m_gate: warashina_2004__calcium_dependent_potassium_channel_m_gate(m, Ca0, time_); // Assignment Rules: i_SK := g_SK * power(m, 2.0) * (V - E_K); // Variable initializations: g_SK = 3.0; V = ; E_K = ; end model warashina_2004__buffered_calcium_diffusion(Bu, CaBu, k1b, k2b, kfc, kbc, delta_r, Ai2, vol_i) // Assignment Rules: kfc := (DCa * Ai2) / (delta_r * vol_i); kbc := (DCa * Ai2) / (delta_r * vol_i); // Variable initializations: Bu = ; CaBu = ; k1b = 100.0; k2b = 10.0; Cai = ; DCa = 0.22; TBu = 4.0; delta_r = ; Ai2 = ; vol_i = ; end model warashina_2004__calcium_extrusion(i_ex, Ca0) // Assignment Rules: i_ex := Vmax * (Ca0 / (Kex + Ca0)) - Vmax * (Ca_rest / (Kex + Ca_rest)); // Variable initializations: Vmax = 3.0; Kex = 830.0; Ca_rest = 100.0; Ca0 = ; end model warashina_2004__calcium_triggered_exocytosis(Ca0) // Assignment Rules: SR := k2 * B; k1f := a1 * (Ca0 / (b1 + Ca0)); k1b := a2; k2 := a3 * power(Ca0, 3.0); C := B * k2; // Variable initializations: a1 = 9.0E-6; a2 = 5.5E-6; a3 = 2.3E-5; b1 = 1.2; B = ; A = 2000.0; Ca0 = ; end model warashina_2004__calcium_indicator(CaDy, Dy, k1d, k2d, delta_r, Ai2, vol_i) // Assignment Rules: FDy := (1.0 - F0) * FCaDy + F0; kfd := (Ddy * Ai2) / (delta_r * vol_i); kbd := (Ddy * Ai2) / (delta_r * vol_i); // Variable initializations: CaDy = ; Dy = ; k1d = 500.0; k2d = 0.12; Dyi2 = ; Cai = ; FCaDy = ; TDy = 5.0; Ddy = 0.05; Dkd = 240.0; F0 = 0.36; delta_r = ; Ai2 = ; vol_i = ; end model warashina_2004__calcium_concentration(Ca0, time_, i_Ca, i_ex, CaBu, Bu, CaDy, Dy, F, k1d, k2d, k1b, k2b, kfc, kbc) // Rate Rules: Ca0' = (kbc * Ca1 + k2b * CaBu + k2d * CaDy) - (((i_Ca + i_ex) * A0) / (2.0 * F * vol0) + kfc * Ca0 + k1b * Bu * Ca0 + k1d * Dy * Ca0); // Variable initializations: Ca0 = 0.1; A0 = 706.86; vol0 = ; Ca1 = ; time_ = ; i_Ca = ; i_ex = ; CaBu = ; Bu = ; CaDy = ; Dy = ; F = ; k1d = ; k2d = ; k1b = ; k2b = ; kfc = ; kbc = ; end model warashina_2004__model_parameters(R, T, F, delta_r, Ai2, vol_i, E_K) // Assignment Rules: delta_r := diameter / (2.0 * (Nc - 1.0)); // Variable initializations: R = 8.3144; T = 310.15; F = 96485; Ai2 = ; vol_i = 1767.15; E_K = -80.0; diameter = 15.0; Nc = 6.0; end model *warashina_2004____main() // Sub-modules, and any changes to those submodules: environment: warashina_2004__environment(time_); membrane: warashina_2004__membrane(V, time_, i_Na, i_sp, i_K, i_l, i_Ca, i_SK, i_ex); excitatory_synapse: warashina_2004__excitatory_synapse(i_sp, V, time_); sodium_channel: warashina_2004__sodium_channel(i_Na, time_, V, m, h); potassium_channel: warashina_2004__potassium_channel(i_K, time_, V, E_K, n); leak_channel: warashina_2004__leak_channel(i_l, V); calcium_channel: warashina_2004__calcium_channel(i_Ca, time_, V, Ca0, R, T, F, m0, h0); calcium_dependent_potassium_channel: warashina_2004__calcium_dependent_potassium_channel(i_SK, time_, V, Ca0, E_K, m1); buffered_calcium_diffusion: warashina_2004__buffered_calcium_diffusion(Bu, CaBu, k1b, k2b, kfc, kbc, delta_r, Ai2, vol_i); calcium_extrusion: warashina_2004__calcium_extrusion(i_ex, Ca0); calcium_triggered_exocytosis: warashina_2004__calcium_triggered_exocytosis(Ca0); calcium_indicator: warashina_2004__calcium_indicator(CaDy, Dy, k1d, k2d, delta_r, Ai2, vol_i); calcium_concentration: warashina_2004__calcium_concentration(Ca0, time_, i_Ca, i_ex, CaBu, Bu, CaDy, Dy, F, k1d, k2d, k1b, k2b, kfc, kbc); model_parameters: warashina_2004__model_parameters(R, T, F, delta_r, Ai2, vol_i, E_K); end