Model Mathematics

Component: environment

Component: membrane

I_Stim=stim_amplitudeiftime-⌊timestim_period⌋⁢stim_period≥0∧time-⌊timestim_period⌋⁢stim_period≦stim_duration0otherwise FVRT=F⁢VR⁢T FVRT_Ca=2⁢FVRT 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=-1.5⁢hinch_I_LCC⁢2⁢V_myo_uL⁢F I_NaCa=hinch_I_NaCa⁢V_myo_uL⁢F I_pCa=hinch_I_pCa⁢2⁢V_myo_uL⁢F I_CaB=-hinch_I_CaB⁢2⁢V_myo_uL⁢F I_RyR=1.5⁢hinch_I_RyR

Component: sodium_potassium_pump

sigma=ⅇNa_o67.3-17 i_NaK=i_NaK_max⁢11+0.1245⁢ⅇ-0.1⁢V⁢FR⁢T+0.0365⁢sigma⁢ⅇ-V⁢FR⁢T⁢K_oK_o+K_m_K⁢11+K_m_NaNa_i4

Component: intracellular_ion_concentrations

Ca_b=Ca_TRPN_Max-TRPN ddtimeNa_i=-I_Na+I_B_Na+I_NaCa⁢3+I_NaK⁢3+I_f_Na⁢1V_myo_uL⁢F ddtimeK_i=-I_Stim+I_ss+I_B_K+I_t+I_K1+I_f_K+I_NaK⁢-2⁢1V_myo_uL⁢F ddtimeTRPN=I_TRPN ddtimeCa_i=beta_CMDN⁢I_RyR-I_SERCA+I_SR+I_TRPN--2⁢I_NaCa+I_pCa+I_CaB+I_LCC2⁢V_myo_uL⁢F ddtimeCa_SR=V_myo_uLV_SR_uL⁢-I_RyR+I_SERCA-I_SR

Component: environment

Component: membrane

stim_period=1iftime≥5∧time≦101otherwise i_Stim=stim_amplitudeiftime-⌊timestim_period⌋⁢stim_period≥0.02∧time-⌊timestim_period⌋⁢stim_period≦stim_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=1.33⁢g_Na E_Na=R⁢TF⁢ln⁡Na_oNa_i i_Na=g_Na_endo⁢m3⁢h⁢j⁢V-E_Na

Component: sodium_current_m_gate

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

Component: sodium_current_h_gate

h_infinity=11+ⅇV+76.16.07 tau_h=0.0004537⁢1+ⅇ-V+10.6611.1ifV≥-400.003490.135⁢ⅇ-V+806.8+3.56⁢ⅇ0.079⁢V+310000⁢ⅇ0.35⁢Votherwise ddtimeh=h_infinity-htau_h

Component: sodium_current_j_gate

j_infinity=11+ⅇV+76.16.07 tau_j=0.01163⁢1+ⅇ-0.1⁢V+32ⅇ-0.0000002535⁢VifV≥-400.00349V+37.781+ⅇ0.311⁢V+79.23⁢-127140⁢ⅇ0.2444⁢V-0.00003474⁢ⅇ-0.04391⁢V+0.1212⁢ⅇ-0.01052⁢V1+ⅇ-0.1378⁢V+40.14otherwise ddtimej=j_infinity-jtau_j

Component: L_type_Ca_channel

i_Ca_L=g_Ca_L⁢d⁢0.9+Ca_inact10⁢f_11+0.1-Ca_inact10⁢f_12⁢V-E_Ca_L

Component: L_type_Ca_channel_d_gate

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

Component: L_type_Ca_channel_f_11_gate

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

Component: L_type_Ca_channel_f_12_gate

f_12_infinity=11+ⅇV+26.75.4 tau_f_12=0.041⁢ⅇ-V+47122+0.081+ⅇV+55-5+0.0151+ⅇV+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=0.4647⁢g_t E_K=R⁢TF⁢ln⁡K_oK_i i_t=g_t_endo⁢r⁢a_endo⁢s+b_endo⁢s_slow⁢V-E_K

Component: Ca_independent_transient_outward_K_current_r_gate

r_infinity=11+ⅇV+10.6-11.42 tau_r=145.16⁢ⅇ0.03577⁢V+50+98.9⁢ⅇ-0.1⁢V+38 ddtimer=r_infinity-rtau_r

Component: Ca_independent_transient_outward_K_current_s_gate

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

Component: Ca_independent_transient_outward_K_current_s_slow_gate

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

Component: steady_state_outward_K_current

i_ss=g_ss⁢r_ss⁢s_ss⁢V-E_K

Component: steady_state_outward_K_current_r_ss_gate

r_ss_infinity=11+ⅇV+11.5-11.82 tau_r_ss=1045.16⁢ⅇ0.03577⁢V+50+98.9⁢ⅇ-0.1⁢V+38 ddtimer_ss=r_ss_infinity-r_sstau_r_ss

Component: steady_state_outward_K_current_s_ss_gate

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

Component: inward_rectifier

i_K1=48ⅇV+3725+ⅇV+37-25+10⁢0.0011+ⅇV-E_K+76.77-17+g_K1⁢V-E_K+1.731+ⅇ1.613⁢F⁢V-E_K+1.73R⁢T⁢1+ⅇK_o-0.9988-0.124

Component: hyperpolarisation_activated_current

f_K=1-f_Na i_f_Na=g_f⁢y⁢f_Na⁢V-E_Na i_f_K=g_f⁢y⁢f_K⁢V-E_K i_f=i_f_Na+i_f_K

Component: hyperpolarisation_activated_current_y_gate

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

Component: background_currents

i_B_Na=g_B_Na⁢V-E_Na i_B_Ca=g_B_Ca⁢V-E_Ca i_B_K=g_B_K⁢V-E_K i_B=i_B_Na+i_B_Ca+i_B_K

Component: sodium_potassium_pump

sigma=ⅇNa_o67.3-17 i_NaK=i_NaK_max⁢11+0.1245⁢ⅇ-0.1⁢V⁢FR⁢T+0.0365⁢sigma⁢ⅇ-V⁢FR⁢T⁢K_oK_o+K_m_K⁢11+K_m_NaNa_i1.5

Component: sarcolemmal_calcium_pump_current

i_Ca_P=i_Ca_P_max⁢Ca_iCa_i+0.0004

Component: Na_Ca_ion_exchanger_current

i_NaCa=K_NaCa⁢Na_i3⁢Ca_o⁢ⅇ0.03743⁢V⁢gamma_NaCa-Na_o3⁢Ca_i⁢ⅇ0.03743⁢V⁢gamma_NaCa-11+d_NaCa⁢Ca_i⁢Na_o3+Ca_o⁢Na_i3

Component: SR_Ca_release_channel

ddtimeP_C1=-k_a_plus⁢Ca_ssn⁢P_C1+k_a_minus⁢P_O1 ddtimeP_O1=k_a_plus⁢Ca_ssn⁢P_C1-k_a_minus⁢P_O1+k_b_plus⁢Ca_ssm⁢P_O1+k_c_plus⁢P_O1+k_b_minus⁢P_O2+k_c_minus⁢P_C2 ddtimeP_O2=k_b_plus⁢Ca_ssm⁢P_O1-k_b_minus⁢P_O2 ddtimeP_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

fb=Ca_iK_fbN_fb rb=Ca_NSRK_rbN_rb J_up=K_SR⁢Vmaxf⁢fb-Vmaxr⁢rb1+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_plus⁢Ca_i⁢HTRPN_tot-HTRPNCa-k_htrpn_minus⁢HTRPNCa ddtimeHTRPNCa=J_HTRPNCa J_LTRPNCa=k_ltrpn_plus⁢Ca_i⁢LTRPN_tot-LTRPNCa-k_ltrpn_minus⁢LTRPNCa ddtimeLTRPNCa=J_LTRPNCa J_trpn=J_HTRPNCa+J_LTRPNCa

Component: intracellular_ion_concentrations

beta_i=11+CMDN_tot⁢K_mCMDNK_mCMDN+Ca_i2+EGTA_tot⁢K_mEGTAK_mEGTA+Ca_i2 beta_SS=11+CMDN_tot⁢K_mCMDNK_mCMDN+Ca_ss2 beta_JSR=11+CSQN_tot⁢K_mCSQNK_mCSQN+Ca_JSR2 ddtimeCa_i=beta_i⁢J_xfer-J_up+J_trpn+i_B_Ca-2⁢i_NaCa+i_Ca_P⁢12⁢V_myo⁢F ddtimeNa_i=-i_Na+i_B_Na+i_NaCa⁢3+i_NaK⁢3+i_f_Na⁢1V_myo⁢F ddtimeK_i=-i_Stim+i_ss+i_B_K+i_t+i_K1+i_f_K+i_NaK⁢-2⁢1V_myo⁢F ddtimeCa_ss=beta_SS⁢J_rel⁢V_JSRV_SS-J_xfer⁢V_myoV_SS-i_Ca_L⁢12⁢V_SS⁢F ddtimeCa_JSR=beta_JSR⁢J_tr-J_rel ddtimeCa_NSR=J_up⁢V_myoV_NSR-J_tr⁢V_JSRV_NSR

Component: standard_ionic_concentrations

Component: environment

Component: cell_geometry

Component: membrane

FVRT=F⁢VR⁢T FVRT_Ca=2⁢FVRT V=0iftime≥0∧time≦200-80otherwise

Component: CaRU

Component: CaRU_Transitions

expVL=ⅇV-V_Ldel_VL t_R=1.17⁢t_L alpha_p=expVLt_L⁢expVL+1 alpha_m=phi_Lt_L beta_poc=C_oc2t_R⁢C_oc2+K_RyR2 beta_pcc=Ca_i2t_R⁢Ca_i2+K_RyR2 beta_m=phi_Rt_R epsilon_pco=C_co⁢expVL+atau_L⁢K_L⁢expVL+1 epsilon_pcc=Ca_i⁢expVL+atau_L⁢K_L⁢expVL+1 epsilon_m=b⁢expVL+atau_L⁢b⁢expVL+a mu_poc=C_oc2+c⁢K_RyR2tau_R⁢C_oc2+K_RyR2 mu_pcc=Ca_i2+c⁢K_RyR2tau_R⁢Ca_i2+K_RyR2 mu_moc=theta_R⁢d⁢C_oc2+c⁢K_RyR2tau_R⁢d⁢C_oc2+c⁢K_RyR2 mu_mcc=theta_R⁢d⁢Ca_i2+c⁢K_RyR2tau_R⁢d⁢Ca_i2+c⁢K_RyR2

Component: DS_Calcium_Concentrations

C_cc=Ca_i C_co=Ca_i+J_Rg_D⁢Ca_SR1+J_Rg_D C_oc=Ca_i+J_Lg_D⁢Ca_o⁢FVRT_Ca⁢ⅇ-FVRT_Ca1-ⅇ-FVRT_Ca1+J_Lg_D⁢FVRT_Ca1-ⅇ-FVRT_Caif|FVRT_Ca|>0.000000001Ca_i+J_Lg_D⁢Ca_o1+J_Lg_Dotherwise C_oo=Ca_i+J_Rg_D⁢Ca_SR+J_Lg_D⁢Ca_o⁢FVRT_Ca⁢ⅇ-FVRT_Ca1-ⅇ-FVRT_Ca1+J_Rg_D+J_Lg_D⁢FVRT_Ca1-ⅇ-FVRT_Caif|FVRT_Ca|>0.000000001Ca_i+J_Rg_D⁢Ca_SR+J_Lg_D⁢Ca_o1+J_Rg_D+J_Lg_Dotherwise

Component: LCC_and_RyR_fluxes

J_Rco=J_R⁢Ca_SR-Ca_i1+J_Rg_D J_Roo=J_R⁢Ca_SR-Ca_i+J_Lg_D⁢FVRT_Ca1-ⅇ-FVRT_Ca⁢Ca_SR-Ca_o⁢ⅇ-FVRT_Ca1+J_Rg_D+J_Lg_D⁢FVRT_Ca1-ⅇ-FVRT_Caif|FVRT_Ca|>0.00001J_R⁢Ca_SR-Ca_i+J_Lg_D⁢0.000011-ⅇ-0.00001⁢Ca_SR-Ca_o⁢ⅇ-0.000011+J_Rg_D+J_Lg_D⁢0.000011-ⅇ-0.00001otherwise J_Loc=J_L⁢FVRT_Ca1-ⅇ-FVRT_Ca⁢Ca_o⁢ⅇ-FVRT_Ca-Ca_i1+J_Lg_D⁢FVRT_Ca1-ⅇ-FVRT_Caif|FVRT_Ca|>0.00001J_L⁢0.000011-ⅇ-0.00001⁢Ca_o⁢ⅇ-0.00001-Ca_i1+J_Lg_D⁢0.000011-ⅇ-0.00001otherwise J_Loo=J_L⁢FVRT_Ca1-ⅇ-FVRT_Ca⁢Ca_o⁢ⅇ-FVRT_Ca-Ca_i+J_Rg_D⁢Ca_o⁢ⅇ-FVRT_Ca-Ca_SR1+J_Rg_D+J_Lg_D⁢FVRT_Ca1-ⅇFVRT_Caif|FVRT_Ca|>0.00001J_L⁢0.000011-ⅇ-0.00001⁢Ca_o⁢ⅇ-0.00001-Ca_i+J_Rg_D⁢Ca_o⁢ⅇ-0.00001-Ca_SR1+J_Rg_D+J_Lg_D⁢0.000011-ⅇ-0.00001otherwise

Component: CaRU_states

denom=alpha_p+alpha_m⁢alpha_m+beta_m+beta_poc⁢beta_m+beta_pcc+alpha_p⁢beta_m+beta_poc y_oc=alpha_p⁢beta_m⁢alpha_p+alpha_m+beta_m+beta_pccdenom y_co=alpha_m⁢beta_pcc⁢alpha_m+beta_m+beta_poc+beta_poc⁢alpha_pdenom y_oo=alpha_p⁢beta_poc⁢alpha_p+beta_m+beta_pcc+beta_pcc⁢alpha_mdenom y_cc=alpha_m⁢beta_m⁢alpha_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_oc⁢mu_poc+y_cc⁢mu_pcc r_2=alpha_p⁢mu_moc+alpha_m⁢mu_mccalpha_p+alpha_m r_3=beta_m⁢mu_pccbeta_m+beta_pcc r_4=mu_mcc r_5=y_co⁢epsilon_pco+y_cc⁢epsilon_pcc r_6=epsilon_m r_7=alpha_m⁢epsilon_pccalpha_p+alpha_m r_8=epsilon_m z_4=1-z_1-z_2-z_3 ddtimez_1=-r_1+r_5⁢z_1+r_2⁢z_2+r_6⁢z_3 ddtimez_2=r_1⁢z_1-r_2+r_7⁢z_2+r_8⁢z_4 ddtimez_3=r_5⁢z_1-r_6+r_3⁢z_3+r_4⁢z_4

Component: RyR_current

J_R1=y_oo⁢J_Roo+J_Rco⁢y_co J_R3=J_Rco⁢beta_pccbeta_m+beta_pcc I_RyR=z_1⁢J_R1+z_3⁢J_R3⁢NV_myo

Component: LCC_current

J_L1=J_Loo⁢y_oo+J_Loc⁢y_oc J_L2=J_Loc⁢alpha_palpha_p+alpha_m I_LCC=z_1⁢J_L1+z_2⁢J_L2⁢NV_myo

Component: Na_Ca_Exchanger

I_NaCa=g_NCX⁢ⅇeta⁢FVRT⁢Na_i3⁢Ca_o-ⅇeta-1⁢FVRT⁢Na_o3⁢Ca_iNa_o3+K_mNa3⁢Ca_o+K_mCa⁢1+k_sat⁢ⅇeta-1⁢FVRT

Component: SERCA

I_SERCA=g_SERCA⁢Ca_i2K_SERCA2+Ca_i2

Component: Sarcolemmal_Ca_pump

I_pCa=g_pCa⁢Ca_iK_mpCa+Ca_i

Component: Background_Ca_current

E_Ca=R⁢T2⁢F⁢ln⁡Ca_oCa_i I_CaB=g_CaB⁢E_Ca-V

Component: SR_Ca_leak_current

I_SR=g_SRl⁢Ca_SR-Ca_i

Component: troponin_Ca_buffer

I_TRPN=k_m_TRPN⁢B_TRPN-TRPN-k_p_TRPN⁢TRPN⁢Ca_i

Component: calmodulin_Ca_buffer

beta_CMDN=1+k_CMDN⁢B_CMDNk_CMDN+Ca_i2-1

Component: intracellular_ion_concentrations

ddtimeTRPN=I_TRPN ddtimeCa_i=beta_CMDN⁢I_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_SR⁢V_SRV_myo

Component: extracellular_ion_concentrations

Component: environment

Component: intracellular_ion_concentrations

Ca_b=Ca_TRPN_Max-TRPN ddtimeTRPN=J_TRPN Ca_i=1000⁢1.8433e-7iftime<11000⁢1.055⁢time10003-0.03507⁢time10002+0.0003992⁢time1000-1.356e-6iftime≥10∧time<151000⁢0.014⁢time10003-0.002555⁢time10002+0.0001494⁢time1000-1.428e-6iftime≥15∧time<551000⁢1.739e-5⁢time10003-3.209e-6⁢time10002-5.689e-6⁢time1000+1.719e-6iftime≥55∧time<2501000⁢0.0001321⁢time10004-0.0002197⁢time10003+0.0001374⁢time10002-3.895e-5⁢time1000+4.441e-6iftime≥250∧time<4901000⁢1.2148e-7otherwise

Component: thinfilaments

Component: tropomyosin

K_2=alpha_r2⁢z_pn_Relz_pn_Rel+K_zn_Rel⁢1-n_Rel⁢K_zn_Relz_pn_Rel+K_zn_Rel K_1=alpha_r2⁢z_pn_Rel-1⁢n_Rel⁢K_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_50ref⁢1+beta_1⁢lambda-1 Ca_TRPN_50=Ca_50⁢Ca_TRPN_MaxCa_50+k_Ref_offk_on⁢1-1+beta_0⁢lambda-1⁢0.5gamma_trpn alpha_Tm=alpha_0⁢Ca_bCa_TRPN_50n_Hill beta_Tm=alpha_r1+alpha_r2⁢zn_Rel-1zn_Rel+K_zn_Rel ddtimez=alpha_Tm⁢1-z-beta_Tm⁢z

Component: troponin

k_off=k_Ref_off⁢1-Tensiongamma_trpn⁢T_refif1-Tensiongamma_trpn⁢T_ref>0.1k_Ref_off⁢0.1otherwise J_TRPN=Ca_TRPN_Max-TRPN⁢k_off-Ca_i⁢TRPN⁢k_on

Component: Myofilaments

ExtensionRatio=1iftime>3e51otherwise lambda_prev=ExtensionRatio dExtensionRatiodt=0 lambda=ExtensionRatioifExtensionRatio>0.8∧ExtensionRatio≦1.151.15ifExtensionRatio>1.150.8otherwise

Component: filament_overlap

overlap=1+beta_0⁢lambda-1

Component: length_independent_tension

T_Base=T_ref⁢zz_max

Component: isometric_tension

T_0=T_Base⁢overlap

Component: Cross_Bridges

Q=Q_1+Q_2+Q_3 Tension=T_0⁢a⁢Q+11-QifQ<0T_0⁢1+a+2⁢Q1+Qotherwise ddtimeQ_1=A_1⁢dExtensionRatiodt-alpha_1⁢Q_1 ddtimeQ_2=A_2⁢dExtensionRatiodt-alpha_2⁢Q_2 ddtimeQ_3=A_3⁢dExtensionRatiodt-alpha_3⁢Q_3