Model Mathematics

Component: environment

Component: membrane

I_Stim=stim_amplitudeiftime-timestim_periodstim_period0time-timestim_periodstim_periodstim_duration0otherwise FVRT=FVRT FVRT_Ca=2FVRT ddtimeV=-I_Na+I_t+I_ss+I_f+I_K1+I_B_Na+I_B_K+I_NaK+I_Stim+I_CaB+I_NaCa+I_pCa+I_LCCCm

Component: cell_geometry

Component: convert_hinch

I_LCC=-1.5hinch_I_LCC2V_myo_uLF I_NaCa=hinch_I_NaCaV_myo_uLF I_pCa=hinch_I_pCa2V_myo_uLF I_CaB=-hinch_I_CaB2V_myo_uLF I_RyR=1.5hinch_I_RyR

Component: sodium_potassium_pump

sigma=Na_o67.3-17 i_NaK=i_NaK_max11+0.1245-0.1VFRT+0.0365sigma-VFRTK_oK_o+K_m_K11+K_m_NaNa_i4

Component: intracellular_ion_concentrations

Ca_b=Ca_TRPN_Max-TRPN ddtimeNa_i=-I_Na+I_B_Na+I_NaCa3+I_NaK3+I_f_Na1V_myo_uLF ddtimeK_i=-I_Stim+I_ss+I_B_K+I_t+I_K1+I_f_K+I_NaK-21V_myo_uLF ddtimeTRPN=I_TRPN ddtimeCa_i=beta_CMDNI_RyR-I_SERCA+I_SR+I_TRPN--2I_NaCa+I_pCa+I_CaB+I_LCC2V_myo_uLF ddtimeCa_SR=V_myo_uLV_SR_uL-I_RyR+I_SERCA-I_SR

Component: environment

Component: membrane

stim_period=1iftime5time101otherwise i_Stim=stim_amplitudeiftime-timestim_periodstim_period0.02time-timestim_periodstim_periodstim_duration+0.020otherwise ddtimeV=-i_Na+i_Ca_L+i_t+i_ss+i_f+i_K1+i_B+i_NaK+i_NaCa+i_Ca_P+i_StimCm

Component: sodium_current

g_Na_endo=1.33g_Na E_Na=RTFlnNa_oNa_i i_Na=g_Na_endom3hjV-E_Na

Component: sodium_current_m_gate

m_infinity=11+V+45-6.5 tau_m=0.001360.32V+47.131--0.1V+47.13+0.08-V11 ddtimem=m_infinity-mtau_m

Component: sodium_current_h_gate

h_infinity=11+V+76.16.07 tau_h=0.00045371+-V+10.6611.1ifV-400.003490.135-V+806.8+3.560.079V+3100000.35Votherwise ddtimeh=h_infinity-htau_h

Component: sodium_current_j_gate

j_infinity=11+V+76.16.07 tau_j=0.011631+-0.1V+32-0.0000002535VifV-400.00349V+37.781+0.311V+79.23-1271400.2444V-0.00003474-0.04391V+0.1212-0.01052V1+-0.1378V+40.14otherwise ddtimej=j_infinity-jtau_j

Component: L_type_Ca_channel

i_Ca_L=g_Ca_Ld0.9+Ca_inact10f_11+0.1-Ca_inact10f_12V-E_Ca_L

Component: L_type_Ca_channel_d_gate

d_infinity=11+V+15.3-5 tau_d=0.00305-0.0045V+72+0.00105-0.002V-182+0.00025 ddtimed=d_infinity-dtau_d

Component: L_type_Ca_channel_f_11_gate

f_11_infinity=11+V+26.75.4 tau_f_11=0.105-V+45122+0.041+-V+2525+0.0151+V+7525+0.0017 ddtimef_11=f_11_infinity-f_11tau_f_11

Component: L_type_Ca_channel_f_12_gate

f_12_infinity=11+V+26.75.4 tau_f_12=0.041-V+47122+0.081+V+55-5+0.0151+V+7525+0.0017 ddtimef_12=f_12_infinity-f_12tau_f_12

Component: L_type_Ca_channel_Ca_inact_gate

Ca_inact_infinity=11+Ca_ss0.01 ddtimeCa_inact=Ca_inact_infinity-Ca_inacttau_Ca_inact

Component: Ca_independent_transient_outward_K_current

g_t_endo=0.4647g_t E_K=RTFlnK_oK_i i_t=g_t_endora_endos+b_endos_slowV-E_K

Component: Ca_independent_transient_outward_K_current_r_gate

r_infinity=11+V+10.6-11.42 tau_r=145.160.03577V+50+98.9-0.1V+38 ddtimer=r_infinity-rtau_r

Component: Ca_independent_transient_outward_K_current_s_gate

s_infinity=11+V+45.36.8841 tau_s_endo=0.55-V+70252+0.049 ddtimes=s_infinity-stau_s_endo

Component: Ca_independent_transient_outward_K_current_s_slow_gate

s_slow_infinity=11+V+45.36.8841 tau_s_slow_endo=3.3-V+7030V+7030+0.049 ddtimes_slow=s_slow_infinity-s_slowtau_s_slow_endo

Component: steady_state_outward_K_current

i_ss=g_ssr_sss_ssV-E_K

Component: steady_state_outward_K_current_r_ss_gate

r_ss_infinity=11+V+11.5-11.82 tau_r_ss=1045.160.03577V+50+98.9-0.1V+38 ddtimer_ss=r_ss_infinity-r_sstau_r_ss

Component: steady_state_outward_K_current_s_ss_gate

s_ss_infinity=11+V+87.510.3 tau_s_ss=2.1 ddtimes_ss=s_ss_infinity-s_sstau_s_ss

Component: inward_rectifier

i_K1=48V+3725+V+37-25+100.0011+V-E_K+76.77-17+g_K1V-E_K+1.731+1.613FV-E_K+1.73RT1+K_o-0.9988-0.124

Component: hyperpolarisation_activated_current

f_K=1-f_Na i_f_Na=g_fyf_NaV-E_Na i_f_K=g_fyf_KV-E_K i_f=i_f_Na+i_f_K

Component: hyperpolarisation_activated_current_y_gate

y_infinity=11+V+138.610.48 tau_y=10.11885V+8028.37+0.5623V+80-14.19 ddtimey=y_infinity-ytau_y

Component: background_currents

i_B_Na=g_B_NaV-E_Na i_B_Ca=g_B_CaV-E_Ca i_B_K=g_B_KV-E_K i_B=i_B_Na+i_B_Ca+i_B_K

Component: sodium_potassium_pump

sigma=Na_o67.3-17 i_NaK=i_NaK_max11+0.1245-0.1VFRT+0.0365sigma-VFRTK_oK_o+K_m_K11+K_m_NaNa_i1.5

Component: sarcolemmal_calcium_pump_current

i_Ca_P=i_Ca_P_maxCa_iCa_i+0.0004

Component: Na_Ca_ion_exchanger_current

i_NaCa=K_NaCaNa_i3Ca_o0.03743Vgamma_NaCa-Na_o3Ca_i0.03743Vgamma_NaCa-11+d_NaCaCa_iNa_o3+Ca_oNa_i3

Component: SR_Ca_release_channel

ddtimeP_C1=-k_a_plusCa_ssnP_C1+k_a_minusP_O1 ddtimeP_O1=k_a_plusCa_ssnP_C1-k_a_minusP_O1+k_b_plusCa_ssmP_O1+k_c_plusP_O1+k_b_minusP_O2+k_c_minusP_C2 ddtimeP_O2=k_b_plusCa_ssmP_O1-k_b_minusP_O2 ddtimeP_C2=k_c_plusP_O1-k_c_minusP_C2 J_rel=v1P_O1+P_O2Ca_JSR-Ca_ss

Component: SERCA2a_pump

fb=Ca_iK_fbN_fb rb=Ca_NSRK_rbN_rb J_up=K_SRVmaxffb-Vmaxrrb1+fb+rb

Component: intracellular_and_SR_Ca_fluxes

J_tr=Ca_NSR-Ca_JSRtau_tr J_xfer=Ca_ss-Ca_itau_xfer J_HTRPNCa=k_htrpn_plusCa_iHTRPN_tot-HTRPNCa-k_htrpn_minusHTRPNCa ddtimeHTRPNCa=J_HTRPNCa J_LTRPNCa=k_ltrpn_plusCa_iLTRPN_tot-LTRPNCa-k_ltrpn_minusLTRPNCa ddtimeLTRPNCa=J_LTRPNCa J_trpn=J_HTRPNCa+J_LTRPNCa

Component: intracellular_ion_concentrations

beta_i=11+CMDN_totK_mCMDNK_mCMDN+Ca_i2+EGTA_totK_mEGTAK_mEGTA+Ca_i2 beta_SS=11+CMDN_totK_mCMDNK_mCMDN+Ca_ss2 beta_JSR=11+CSQN_totK_mCSQNK_mCSQN+Ca_JSR2 ddtimeCa_i=beta_iJ_xfer-J_up+J_trpn+i_B_Ca-2i_NaCa+i_Ca_P12V_myoF ddtimeNa_i=-i_Na+i_B_Na+i_NaCa3+i_NaK3+i_f_Na1V_myoF ddtimeK_i=-i_Stim+i_ss+i_B_K+i_t+i_K1+i_f_K+i_NaK-21V_myoF ddtimeCa_ss=beta_SSJ_relV_JSRV_SS-J_xferV_myoV_SS-i_Ca_L12V_SSF ddtimeCa_JSR=beta_JSRJ_tr-J_rel ddtimeCa_NSR=J_upV_myoV_NSR-J_trV_JSRV_NSR

Component: standard_ionic_concentrations

Component: environment

Component: cell_geometry

Component: membrane

FVRT=FVRT FVRT_Ca=2FVRT V=0iftime0time200-80otherwise

Component: CaRU

Component: CaRU_Transitions

expVL=V-V_Ldel_VL t_R=1.17t_L alpha_p=expVLt_LexpVL+1 alpha_m=phi_Lt_L beta_poc=C_oc2t_RC_oc2+K_RyR2 beta_pcc=Ca_i2t_RCa_i2+K_RyR2 beta_m=phi_Rt_R epsilon_pco=C_coexpVL+atau_LK_LexpVL+1 epsilon_pcc=Ca_iexpVL+atau_LK_LexpVL+1 epsilon_m=bexpVL+atau_LbexpVL+a mu_poc=C_oc2+cK_RyR2tau_RC_oc2+K_RyR2 mu_pcc=Ca_i2+cK_RyR2tau_RCa_i2+K_RyR2 mu_moc=theta_RdC_oc2+cK_RyR2tau_RdC_oc2+cK_RyR2 mu_mcc=theta_RdCa_i2+cK_RyR2tau_RdCa_i2+cK_RyR2

Component: DS_Calcium_Concentrations

C_cc=Ca_i C_co=Ca_i+J_Rg_DCa_SR1+J_Rg_D C_oc=Ca_i+J_Lg_DCa_oFVRT_Ca-FVRT_Ca1--FVRT_Ca1+J_Lg_DFVRT_Ca1--FVRT_Caif|FVRT_Ca|>0.000000001Ca_i+J_Lg_DCa_o1+J_Lg_Dotherwise C_oo=Ca_i+J_Rg_DCa_SR+J_Lg_DCa_oFVRT_Ca-FVRT_Ca1--FVRT_Ca1+J_Rg_D+J_Lg_DFVRT_Ca1--FVRT_Caif|FVRT_Ca|>0.000000001Ca_i+J_Rg_DCa_SR+J_Lg_DCa_o1+J_Rg_D+J_Lg_Dotherwise

Component: LCC_and_RyR_fluxes

J_Rco=J_RCa_SR-Ca_i1+J_Rg_D J_Roo=J_RCa_SR-Ca_i+J_Lg_DFVRT_Ca1--FVRT_CaCa_SR-Ca_o-FVRT_Ca1+J_Rg_D+J_Lg_DFVRT_Ca1--FVRT_Caif|FVRT_Ca|>0.00001J_RCa_SR-Ca_i+J_Lg_D0.000011--0.00001Ca_SR-Ca_o-0.000011+J_Rg_D+J_Lg_D0.000011--0.00001otherwise J_Loc=J_LFVRT_Ca1--FVRT_CaCa_o-FVRT_Ca-Ca_i1+J_Lg_DFVRT_Ca1--FVRT_Caif|FVRT_Ca|>0.00001J_L0.000011--0.00001Ca_o-0.00001-Ca_i1+J_Lg_D0.000011--0.00001otherwise J_Loo=J_LFVRT_Ca1--FVRT_CaCa_o-FVRT_Ca-Ca_i+J_Rg_DCa_o-FVRT_Ca-Ca_SR1+J_Rg_D+J_Lg_DFVRT_Ca1-FVRT_Caif|FVRT_Ca|>0.00001J_L0.000011--0.00001Ca_o-0.00001-Ca_i+J_Rg_DCa_o-0.00001-Ca_SR1+J_Rg_D+J_Lg_D0.000011--0.00001otherwise

Component: CaRU_states

denom=alpha_p+alpha_malpha_m+beta_m+beta_pocbeta_m+beta_pcc+alpha_pbeta_m+beta_poc y_oc=alpha_pbeta_malpha_p+alpha_m+beta_m+beta_pccdenom y_co=alpha_mbeta_pccalpha_m+beta_m+beta_poc+beta_pocalpha_pdenom y_oo=alpha_pbeta_pocalpha_p+beta_m+beta_pcc+beta_pccalpha_mdenom y_cc=alpha_mbeta_malpha_m+alpha_p+beta_m+beta_pocdenom y_ci=alpha_malpha_p+alpha_m y_oi=alpha_palpha_p+alpha_m y_ic=beta_mbeta_pcc+beta_m y_io=beta_pccbeta_pcc+beta_m y_ii=1-y_oc-y_co-y_oo-y_cc-y_ci-y_ic-y_oi-y_io

Component: CaRU_reduced_states

r_1=y_ocmu_poc+y_ccmu_pcc r_2=alpha_pmu_moc+alpha_mmu_mccalpha_p+alpha_m r_3=beta_mmu_pccbeta_m+beta_pcc r_4=mu_mcc r_5=y_coepsilon_pco+y_ccepsilon_pcc r_6=epsilon_m r_7=alpha_mepsilon_pccalpha_p+alpha_m r_8=epsilon_m z_4=1-z_1-z_2-z_3 ddtimez_1=-r_1+r_5z_1+r_2z_2+r_6z_3 ddtimez_2=r_1z_1-r_2+r_7z_2+r_8z_4 ddtimez_3=r_5z_1-r_6+r_3z_3+r_4z_4

Component: RyR_current

J_R1=y_ooJ_Roo+J_Rcoy_co J_R3=J_Rcobeta_pccbeta_m+beta_pcc I_RyR=z_1J_R1+z_3J_R3NV_myo

Component: LCC_current

J_L1=J_Looy_oo+J_Locy_oc J_L2=J_Localpha_palpha_p+alpha_m I_LCC=z_1J_L1+z_2J_L2NV_myo

Component: Na_Ca_Exchanger

I_NaCa=g_NCXetaFVRTNa_i3Ca_o-eta-1FVRTNa_o3Ca_iNa_o3+K_mNa3Ca_o+K_mCa1+k_sateta-1FVRT

Component: SERCA

I_SERCA=g_SERCACa_i2K_SERCA2+Ca_i2

Component: Sarcolemmal_Ca_pump

I_pCa=g_pCaCa_iK_mpCa+Ca_i

Component: Background_Ca_current

E_Ca=RT2FlnCa_oCa_i I_CaB=g_CaBE_Ca-V

Component: SR_Ca_leak_current

I_SR=g_SRlCa_SR-Ca_i

Component: troponin_Ca_buffer

I_TRPN=k_m_TRPNB_TRPN-TRPN-k_p_TRPNTRPNCa_i

Component: calmodulin_Ca_buffer

beta_CMDN=1+k_CMDNB_CMDNk_CMDN+Ca_i2-1

Component: intracellular_ion_concentrations

ddtimeTRPN=I_TRPN ddtimeCa_i=beta_CMDNI_LCC+I_RyR-I_SERCA+I_SR+I_NaCa-I_pCa+I_CaB+I_TRPN ddtimeCa_SR=V_myoV_SR-I_RyR+I_SERCA-I_SR CaSR_plot=Ca_SRV_SRV_myo

Component: extracellular_ion_concentrations

Component: environment

Component: intracellular_ion_concentrations

Ca_b=Ca_TRPN_Max-TRPN ddtimeTRPN=J_TRPN Ca_i=10001.8433e-7iftime<110001.055time10003-0.03507time10002+0.0003992time1000-1.356e-6iftime10time<1510000.014time10003-0.002555time10002+0.0001494time1000-1.428e-6iftime15time<5510001.739e-5time10003-3.209e-6time10002-5.689e-6time1000+1.719e-6iftime55time<25010000.0001321time10004-0.0002197time10003+0.0001374time10002-3.895e-5time1000+4.441e-6iftime250time<49010001.2148e-7otherwise

Component: thinfilaments

Component: tropomyosin

K_2=alpha_r2z_pn_Relz_pn_Rel+K_zn_Rel1-n_RelK_zn_Relz_pn_Rel+K_zn_Rel K_1=alpha_r2z_pn_Rel-1n_RelK_zn_Relz_pn_Rel+K_zn_Rel2 z_max=alpha_0Ca_TRPN_50Ca_TRPN_Maxn_Hill-K_2alpha_r1+K_1+alpha_0Ca_TRPN_50Ca_TRPN_Maxn_Hill Ca_50=Ca_50ref1+beta_1lambda-1 Ca_TRPN_50=Ca_50Ca_TRPN_MaxCa_50+k_Ref_offk_on1-1+beta_0lambda-10.5gamma_trpn alpha_Tm=alpha_0Ca_bCa_TRPN_50n_Hill beta_Tm=alpha_r1+alpha_r2zn_Rel-1zn_Rel+K_zn_Rel ddtimez=alpha_Tm1-z-beta_Tmz

Component: troponin

k_off=k_Ref_off1-Tensiongamma_trpnT_refif1-Tensiongamma_trpnT_ref>0.1k_Ref_off0.1otherwise J_TRPN=Ca_TRPN_Max-TRPNk_off-Ca_iTRPNk_on

Component: Myofilaments

ExtensionRatio=1iftime>3e51otherwise lambda_prev=ExtensionRatio dExtensionRatiodt=0 lambda=ExtensionRatioifExtensionRatio>0.8ExtensionRatio1.151.15ifExtensionRatio>1.150.8otherwise

Component: filament_overlap

overlap=1+beta_0lambda-1

Component: length_independent_tension

T_Base=T_refzz_max

Component: isometric_tension

T_0=T_Baseoverlap

Component: Cross_Bridges

Q=Q_1+Q_2+Q_3 Tension=T_0aQ+11-QifQ<0T_01+a+2Q1+Qotherwise ddtimeQ_1=A_1dExtensionRatiodt-alpha_1Q_1 ddtimeQ_2=A_2dExtensionRatiodt-alpha_2Q_2 ddtimeQ_3=A_3dExtensionRatiodt-alpha_3Q_3