Model Mathematics

Component: environment

Component: membrane

dd time V =- i_Na + i_Ca + i_Ca_K + i_Kr + i_Ks + i_to1 + i_K1 + i_Kp + i_NaCa + i_NaK + i_p_Ca + i_Na_b + i_Ca_b C_sc

Component: fast_sodium_current

i_Na = g_Na ⁢ m 3.0 ⁢ h ⁢ j ⁢ V - E_Na E_Na = R ⁢ T F ⁢ln⁡ Nao Nai

Component: fast_sodium_current_m_gate

alpha_m = 0.32 ⁢ V + 47.13 1.0 -ⅇ -0.1 ⁢ V + 47.13 beta_m = 0.08 ⁢ⅇ- V 11.0 dd time m = alpha_m ⁢ 1.0 - m - beta_m ⁢ m

Component: fast_sodium_current_h_gate

alpha_h = 0.135 ⁢ⅇ 80.0 + V -6.8 if V < -40.0 0.0 otherwise beta_h = 3.56 ⁢ⅇ 0.079 ⁢ V + 310000.0 ⁢ⅇ 0.35 ⁢ V if V < -40.0 1.0 0.13 ⁢ 1.0 +ⅇ V + 10.66 -11.1 otherwise dd time h = alpha_h ⁢ 1.0 - h - beta_h ⁢ h

Component: fast_sodium_current_j_gate

alpha_j = -127140.0 ⁢ⅇ 0.2444 ⁢ V - 0.00003474 ⁢ⅇ -0.04391 ⁢ V ⁢ V + 37.78 1.0 +ⅇ 0.311 ⁢ V + 79.23 if V < -40.0 0.0 otherwise beta_j = 0.1212 ⁢ⅇ -0.01052 ⁢ V 1.0 +ⅇ -0.1378 ⁢ V + 40.14 if V < -40.0 0.3 ⁢ⅇ -0.0000002535 ⁢ V 1.0 +ⅇ -0.1 ⁢ V + 32.0 otherwise dd time j = alpha_j ⁢ 1.0 - j - beta_j ⁢ j

Component: rapid_activating_delayed_rectifiyer_K_current

E_K = R ⁢ T F ⁢ln⁡ Ko Ki i_Kr = g_Kr ⁢ f_Ko ⁢ R_V ⁢ X_kr ⁢ V - E_K f_Ko = Ko 4.0 R_V = 1.0 1.0 + 1.4945 ⁢ⅇ 0.0446 ⁢ V

Component: rapid_activating_delayed_rectifiyer_K_current_X_kr_gate

dd time X_kr = K12 ⁢ 1.0 - X_kr - K12 ⁢ X_kr K12 =ⅇ -5.495 + 0.169 ⁢ V K21 =ⅇ -7.677 - 0.0128 ⁢ V

Component: slow_activating_delayed_rectifiyer_K_current

i_Ks = g_Ks ⁢ X_ks 2.0 ⁢ V - E_Ks E_Ks = R ⁢ T F ⁢ln⁡ Ko + 0.01833 ⁢ Nao Ki + 0.01833 ⁢ Nai

Component: slow_activating_delayed_rectifiyer_K_current_X_ks_gate

dd time X_ks = X_ks_infinity - X_ks tau_X_ks X_ks_infinity = 1.0 1.0 +ⅇ- V - 24.7 13.6 tau_X_ks = 1.0 0.0000719 ⁢ V - 10.0 1.0 -ⅇ -0.148 ⁢ V - 10.0 + 0.000131 ⁢ V - 10.0 ⅇ 0.0687 ⁢ V - 10.0 - 1.0

Component: transient_outward_potassium_current

i_to1 = i_Kv4_3 + i_Kv1_4

Component: Kv4_3_current

i_Kv4_3 = g_Kv4_3 ⁢ P_open ⁢ V - E_K P_open = P_O + P_OI dd time P_C0 = alpha_i ⁢ P_CI0 + beta_a ⁢ P_C1 - beta_i + 4.0 ⁢ alpha_a ⁢ P_C0 dd time P_C1 = alpha_i b1 ⁢ P_CI1 + 4.0 ⁢ alpha_a ⁢ P_C0 + 2.0 ⁢ beta_a ⁢ P_C2 - f1 ⁢ beta_i + beta_a + 3.0 ⁢ alpha_a ⁢ P_C1 dd time P_C2 = alpha_i b2 ⁢ P_CI2 + 3.0 ⁢ alpha_a ⁢ P_C1 + 3.0 ⁢ beta_a ⁢ P_C3 - f2 ⁢ beta_i + 2.0 ⁢ beta_a + 2.0 ⁢ alpha_a ⁢ P_C2 dd time P_C3 = alpha_i b3 ⁢ P_CI3 + 2.0 ⁢ alpha_a ⁢ P_C2 + 4.0 ⁢ beta_a ⁢ P_O - f3 ⁢ beta_i + 3.0 ⁢ beta_a + alpha_a ⁢ P_C3 dd time P_O = alpha_a ⁢ P_C3 + alpha_i b4 ⁢ P_OI - f4 ⁢ beta_i + 4.0 ⁢ beta_a ⁢ P_O dd time P_CI0 = beta_i ⁢ P_C0 + beta_a f1 ⁢ P_C1 - alpha_i + b1 ⁢ 4.0 ⁢ alpha_a ⁢ P_CI0 dd time P_CI1 = f1 ⁢ 2.0 ⁢ beta_a f2 ⁢ P_CI2 + b1 ⁢ 4.0 ⁢ alpha_a ⁢ P_CI0 + f1 ⁢ beta_i ⁢ P_C1 - b2 ⁢ 3.0 ⁢ alpha_a b1 + alpha_i b1 + beta_a f1 ⁢ P_CI1 dd time P_CI2 = f2 ⁢ 3.0 ⁢ beta_a f3 ⁢ P_CI3 + b2 ⁢ 3.0 ⁢ alpha_a b1 ⁢ P_CI1 + f2 ⁢ beta_i ⁢ P_C2 - b3 ⁢ 2.0 ⁢ alpha_a b2 + alpha_i b2 + f1 ⁢ 2.0 ⁢ beta_a f2 ⁢ P_CI2 dd time P_CI3 = f3 ⁢ 4.0 ⁢ beta_a f4 ⁢ P_OI + b3 ⁢ 2.0 ⁢ alpha_a b2 ⁢ P_CI2 + f3 ⁢ beta_i ⁢ P_C3 - b4 ⁢ alpha_a b3 + alpha_i b3 + f2 ⁢ 3.0 ⁢ beta_a f3 ⁢ P_CI3 dd time P_OI = b4 ⁢ alpha_a b3 ⁢ P_CI3 + f4 ⁢ beta_i ⁢ P_O - alpha_i b4 + f3 ⁢ 4.0 ⁢ beta_a f4 ⁢ P_OI alpha_a = alpha_a0 ⁢ⅇ a_a beta_a = beta_a0 ⁢ⅇ- b_a alpha_i = alpha_i0 ⁢ⅇ- a_i beta_i = beta_i0 ⁢ⅇ b_i

Component: Kv1_4_current

i_Kv1_4 = i_Kv1_4_K + i_Kv1_4_Na i_Kv1_4_K = P_Kv1_4 C_sc ⁢ F 2.0 ⁢ V R ⁢ T ⁢ P_open ⁢ Ki - Ko ⁢ⅇ- V ⁢ F R ⁢ T 1.0 -ⅇ- V ⁢ F R ⁢ T i_Kv1_4_Na = alpha ⁢ P_Kv1_4 C_sc ⁢ F 2.0 ⁢ V R ⁢ T ⁢ P_open ⁢ Ki - Ko ⁢ⅇ- V ⁢ F R ⁢ T 1.0 -ⅇ- V ⁢ F R ⁢ T P_open = P_O + P_OI dd time P_C0 = alpha_i ⁢ P_CI0 + beta_a ⁢ P_C1 - beta_i + 4.0 ⁢ alpha_a ⁢ P_C0 dd time P_C1 = alpha_i b1 ⁢ P_CI1 + 4.0 ⁢ alpha_a ⁢ P_C0 + 2.0 ⁢ beta_a ⁢ P_C2 - f1 ⁢ beta_i + beta_a + 3.0 ⁢ alpha_a ⁢ P_C1 dd time P_C2 = alpha_i b2 ⁢ P_CI2 + 3.0 ⁢ alpha_a ⁢ P_C1 + 3.0 ⁢ beta_a ⁢ P_C3 - f2 ⁢ beta_i + 2.0 ⁢ beta_a + 2.0 ⁢ alpha_a ⁢ P_C2 dd time P_C3 = alpha_i b3 ⁢ P_CI3 + 2.0 ⁢ alpha_a ⁢ P_C2 + 4.0 ⁢ beta_a ⁢ P_O - f3 ⁢ beta_i + 3.0 ⁢ beta_a + alpha_a ⁢ P_C3 dd time P_O = alpha_a ⁢ P_C3 + alpha_i b4 ⁢ P_OI - f4 ⁢ beta_i + 4.0 ⁢ beta_a ⁢ P_O dd time P_CI0 = beta_i ⁢ P_C0 + beta_a f1 ⁢ P_C1 - alpha_i + b1 ⁢ 4.0 ⁢ alpha_a ⁢ P_CI0 dd time P_CI1 = f1 ⁢ 2.0 ⁢ beta_a f2 ⁢ P_CI2 + b1 ⁢ 4.0 ⁢ alpha_a ⁢ P_CI0 + f1 ⁢ beta_i ⁢ P_C1 - b2 ⁢ 3.0 ⁢ alpha_a b1 + alpha_i b1 + beta_a f1 ⁢ P_CI1 dd time P_CI2 = f2 ⁢ 3.0 ⁢ beta_a f3 ⁢ P_CI3 + b2 ⁢ 3.0 ⁢ alpha_a b1 ⁢ P_CI1 + f2 ⁢ beta_i ⁢ P_C2 - b3 ⁢ 2.0 ⁢ alpha_a b2 + alpha_i b2 + f1 ⁢ 2.0 ⁢ beta_a f2 ⁢ P_CI2 dd time P_CI3 = f3 ⁢ 4.0 ⁢ beta_a f4 ⁢ P_OI + b3 ⁢ 2.0 ⁢ alpha_a b2 ⁢ P_CI2 + f3 ⁢ beta_i ⁢ P_C3 - b4 ⁢ alpha_a b3 + alpha_i b3 + f2 ⁢ 3.0 ⁢ beta_a f3 ⁢ P_CI3 dd time P_OI = b4 ⁢ alpha_a b3 ⁢ P_CI3 + f4 ⁢ beta_i ⁢ P_O - alpha_i b4 + f3 ⁢ 4.0 ⁢ beta_a f4 ⁢ P_OI alpha_a = alpha_a0 ⁢ⅇ a_a beta_a = beta_a0 ⁢ⅇ- b_a alpha_i = alpha_i0 ⁢ⅇ- a_i beta_i = beta_i0 ⁢ⅇ b_i

Component: time_independent_potassium_current

i_K1 = g_K1 ⁢ K1_infinity_V ⁢ Ko Ko + K_mK1 ⁢ V - E_K

Component: time_independent_potassium_current_K1_gate

K1_infinity_V = 1.0 2.0 +ⅇ 1.5 ⁢ F R ⁢ T ⁢ V - E_K

Component: plateau_potassium_current

i_Kp = g_Kp ⁢ Kp_V ⁢ V - E_K

Component: plateau_potassium_current_Kp_gate

Kp_V = 1.0 1.0 +ⅇ 7.488 - V 5.98

Component: Na_Ca_exchanger

i_NaCa = K_NaCa ⁢ 5000.0 K_mNa 3.0 + Nao 3.0 ⁢ 1.0 K_mCa + Cao ⁢ 1.0 1.0 + K_sat ⁢ⅇ eta - 1.0 ⁢ V ⁢ F R ⁢ T ⁢ⅇ eta ⁢ V ⁢ F R ⁢ T ⁢ Nai 3.0 ⁢ Cao -ⅇ eta - 1.0 ⁢ V ⁢ F R ⁢ T ⁢ Nao 3.0 ⁢ Cai

Component: sodium_potassium_pump

f_NaK = 1.0 1.0 + 0.1245 ⁢ⅇ -0.1 ⁢ V ⁢ F R ⁢ T + 0.0365 ⁢ sigma ⁢ⅇ- V ⁢ F R ⁢ T sigma = 1.0 7.0 ⁢ⅇ Nao 67.3 - 1.0 i_NaK = I_NaK ⁢ f_NaK ⁢ 1.0 1.0 + K_mNai Nai 1.5 ⁢ Ko Ko + K_mKo

Component: sarcolemmal_calcium_pump

i_p_Ca = I_pCa ⁢ Cai K_mpCa + Cai

Component: calcium_background_current

E_Ca = R ⁢ T 2.0 ⁢ F ⁢ln⁡ Cao Cai i_Ca_b = g_Cab ⁢ V - E_Ca

Component: sodium_background_current

i_Na_b = g_Nab ⁢ V - E_Na

Component: L_type_Ca_current

i_Ca = i_Ca_max ⁢ y ⁢ O + O_Ca i_Ca_K = p_k C_sc ⁢ y ⁢ O + O_Ca ⁢ V ⁢ F 2.0 R ⁢ T ⁢ Ki ⁢ⅇ V ⁢ F R ⁢ T - Ko ⅇ V ⁢ F R ⁢ T - 1.0 p_k = P_K 1.0 + i_Ca_max i_Ca_half i_Ca_max = P_Ca C_sc ⁢ 4.0 ⁢ V ⁢ F 2.0 R ⁢ T ⁢ 0.001 ⁢ⅇ 2.0 ⁢ V ⁢ F R ⁢ T - 0.341 ⁢ Cao ⅇ 2.0 ⁢ V ⁢ F R ⁢ T - 1.0 alpha = 0.4 ⁢ⅇ V + 2.0 10.0 beta = 0.05 ⁢ⅇ- V + 2.0 13.0 alpha_a = alpha ⁢ a beta_b = beta b gamma = 0.10375 ⁢ Ca_ss dd time C0 = beta ⁢ C1 + omega ⁢ C_Ca0 - 4.0 ⁢ alpha + gamma ⁢ C0 dd time C1 = 4.0 ⁢ alpha ⁢ C0 + 2.0 ⁢ beta ⁢ C2 + omega b ⁢ C_Ca1 - beta + 3.0 ⁢ alpha + gamma ⁢ a ⁢ C1 dd time C2 = 3.0 ⁢ alpha ⁢ C1 + 3.0 ⁢ beta ⁢ C3 + omega b 2.0 ⁢ C_Ca2 - beta ⁢ 2.0 + 2.0 ⁢ alpha + gamma ⁢ a 2.0 ⁢ C2 dd time C3 = 2.0 ⁢ alpha ⁢ C2 + 4.0 ⁢ beta ⁢ C4 + omega b 3.0 ⁢ C_Ca3 - beta ⁢ 3.0 + alpha + gamma ⁢ a 3.0 ⁢ C3 dd time C4 = alpha ⁢ C3 + g ⁢ O + omega b 4.0 ⁢ C_Ca4 - beta ⁢ 4.0 + f + gamma ⁢ a 4.0 ⁢ C4 dd time O = f ⁢ C4 - g ⁢ O dd time C_Ca0 = beta_b ⁢ C_Ca1 + gamma ⁢ C_Ca0 - 4.0 ⁢ alpha_a + omega ⁢ C_Ca0 dd time C_Ca1 = 4.0 ⁢ alpha_a ⁢ C_Ca0 + 2.0 ⁢ beta_b ⁢ C_Ca2 + gamma ⁢ a ⁢ C1 - beta_b + 3.0 ⁢ alpha_a + omega b ⁢ C_Ca1 dd time C_Ca2 = 3.0 ⁢ alpha_a ⁢ C_Ca1 + 3.0 ⁢ beta_b ⁢ C_Ca3 + gamma ⁢ a 2.0 ⁢ C2 - beta_b ⁢ 2.0 + 2.0 ⁢ alpha_a + omega b 2.0 ⁢ C_Ca2 dd time C_Ca3 = 2.0 ⁢ alpha_a ⁢ C_Ca2 + 4.0 ⁢ beta_b ⁢ C_Ca4 + gamma ⁢ a 3.0 ⁢ C3 - beta_b ⁢ 3.0 + alpha_a + omega b 3.0 ⁢ C_Ca3 dd time C_Ca4 = alpha_a ⁢ C_Ca3 + g_ ⁢ O_Ca + gamma ⁢ a 4.0 ⁢ C4 - beta_b ⁢ 4.0 + f_ + omega b 4.0 ⁢ C_Ca4 dd time O_Ca = f_ ⁢ C_Ca4 - g_ ⁢ O_Ca

Component: L_type_Ca_current_y_gate

dd time y = y_infinity - y tau_y y_infinity = 0.8 1.0 +ⅇ V + 12.5 5.0 + 0.2 tau_y = 20.0 + 600.0 1.0 +ⅇ V + 20.0 9.5

Component: RyR_channel

dd time P_C1 =- k_a_plus ⁢ Ca_ss n ⁢ P_C1 + k_a_minus ⁢ P_O1 dd time P_O1 = k_a_plus ⁢ Ca_ss n ⁢ P_C1 - k_a_minus ⁢ P_O1 + k_b_plus ⁢ Ca_ss m ⁢ P_O1 + k_c_plus ⁢ P_O1 + k_b_minus ⁢ P_O2 + k_c_minus ⁢ P_C2 dd time P_O2 = k_b_plus ⁢ Ca_ss m ⁢ P_O1 - k_b_minus ⁢ P_O2 dd time P_C2 = k_c_plus ⁢ P_O1 - k_c_minus ⁢ P_C2 J_rel = v1 ⁢ P_O1 + P_O2 ⁢ Ca_JSR - Ca_ss

Component: SERCA2a_pump

J_up = K_SR ⁢ Vmaxf ⁢ fb - Vmaxr ⁢ rb 1.0 + fb + rb fb = Cai K_fb N_fb rb = Ca_NSR K_rb N_rb

Component: intracellular_Ca_fluxes

J_tr = Ca_NSR - Ca_JSR tau_tr J_xfer = Ca_ss - Cai tau_xfer J_trpn = J_HTRPNCa + J_LTRPNCa J_HTRPNCa =dd time HTRPNCa dd time HTRPNCa = k_htrpn_plus ⁢ Cai ⁢ HTRPN_tot - HTRPNCa - k_htrpn_minus ⁢ HTRPNCa J_LTRPNCa =dd time LTRPNCa dd time LTRPNCa = k_ltrpn_plus ⁢ Cai ⁢ LTRPN_tot - LTRPNCa - k_ltrpn_minus ⁢ LTRPNCa

Component: intracellular_ion_concentrations

dd time Cai = beta_i ⁢ J_xfer - J_up + J_trpn + i_Ca_b - 2.0 ⁢ i_NaCa + i_p_Ca ⁢ A_cap ⁢ C_sc 2.0 ⁢ V_myo ⁢ F dd time Nai =- i_Na + i_Na_b + i_NaCa ⁢ 3.0 + i_NaK ⁢ 3.0 ⁢ A_cap ⁢ C_sc V_myo ⁢ F dd time Ki =- i_Ca_K + i_Kr + i_Ks + i_K1 + i_Kp + i_to1 + i_NaK ⁢ -2.0 ⁢ A_cap ⁢ C_sc V_myo ⁢ F beta_i = 1.0 1.0 + CMDN_tot ⁢ K_mCMDN K_mCMDN + Cai 2.0 beta_SS = 1.0 1.0 + CMDN_tot ⁢ K_mCMDN K_mCMDN + Ca_ss 2.0 beta_JSR = 1.0 1.0 + CSQN_tot ⁢ K_mCSQN K_mCSQN + Ca_JSR 2.0 dd time Ca_ss = beta_SS ⁢ J_rel ⁢ V_JSR V_SS - J_xfer ⁢ V_myo V_SS - i_Ca ⁢ A_cap ⁢ C_sc 2.0 ⁢ V_SS ⁢ F dd time Ca_JSR = beta_JSR ⁢ J_tr - J_rel dd time Ca_NSR = J_up ⁢ V_myo V_NSR - J_tr ⁢ V_JSR V_NSR

Component: standard_ionic_concentrations