// Created by libAntimony v2.8.0 model *Hettling2011() // Compartments and Species: compartment IMS, CYT, cell; species ADPi in IMS, ATPi in IMS, Cri in IMS, PCri in IMS, PCr in CYT, ADP in CYT; species ATP in CYT, Cr in CYT, P_ii in IMS, P_i in CYT; // Assignment Rules: phase := (abs(time - time_Jhyd_step) - (floor(abs(time - time_Jhyd_step)/(60/heartrate_bpm))*60)/heartrate_bpm)/(60/heartrate_bpm); VhydAmp_test := (2*Jhyd_test)/(fracSysUp + fracSysDown); fracDia := 1 - fracSysUp - fracSysDown; VhydAmp_basis := (2*Jhyd_basis)/(fracSysUp + fracSysDown); j_diff_pcr := PSmomPCr*(PCri - PCr); j_diff_atp := PSmomATP*(ATPi - ATP); densyn := 1 + ADPi/Kadp + P_ii/Kpi + (ADPi*P_ii)/(Kadp*Kpi); vatpnorm := tmito_factor*((Jhyd_test - jsyn)/(Jhyd_test - Jhyd_basis)); jsyn := Vmaxsyn*((ADPi*P_ii)/(Kpi*Kadp*densyn)); r_diff_pcr := j_diff_pcr/(j_diff_pcr + j_diff_atp); j_ck_mi := ((VmaxMif*ATPi*Cri)/(KiaMi*KbMi) - (VmaxMib*ADPi*PCri)/(KicMi*KdMi))/(1 + Cri/KibMi + PCri/KidMi + ATPi*(1/KiaMi + Cri/(KiaMi*KbMi)) + ADPi*(1/KicMi + Cri/(KicMi*KibMi) + PCri/(KidMi*((KicMi*KdMi)/KidMi)))); VmaxMif := VmaxMif_full_activity*ck_factor_iaa; VmaxMib := (K_CK_eq*KicMi*KdMi*VmaxMif)/(KiaMi*KbMi); j_ck_mm := ((VmaxMMf*ATP*Cr)/(KiaMM*KbMM) - (VmaxMMb*ADP*PCr)/(KicMM*KdMM))/(1 + Cr/KibMM + PCr/KidMM + ATP*(1/KiaMM + Cr/(KiaMM*KbMM)) + ADP*(1/KicMM + Cr/(KicMM*KibMM) + PCr/(KidMM*((KicMM*KdMM)/KidMM)))); VmaxMMf := VmaxMMf_full_activity*ck_factor_iaa; VmaxMMb := (K_CK_eq*KicMM*KdMM*VmaxMMf)/(KiaMM*KbMM); j_diff_adp := PSmomATP*(ADPi - ADP); j_diff_cr := PSmomCr*(Cri - Cr); j_diff_pi := PSmomPi*(P_ii - P_i); // Rate Rules: tmito' = vatpnorm; // Reactions: Jsyn: P_ii + ADPi -> ATPi; (Vmaxsyn*ADPi*P_ii)/(Kadp*Kpi*(1 + ADPi/Kadp + P_ii/Kpi + (ADPi*P_ii)/(Kadp*Kpi))); J_CK_Mi: ATPi + Cri -> PCri + ADPi; j_ck_mi; J_CK_MM: Cr + ATP -> PCr + ADP; j_ck_mm; Jhyd_reaction: ATP -> ADP + P_i; Jhyd; J_diff_Pi: P_ii -> P_i; j_diff_pi; J_diff_Cr: Cri -> Cr; j_diff_cr; J_diff_ADP: ADPi -> ADP; j_diff_adp; J_diff_PCr: PCri -> PCr; j_diff_pcr; J_diff_ATP: ATPi -> ATP; j_diff_atp; // Events: pulsatile_test: at 0 after time >= time_Jhyd_step && time - last_time_fired > stepsize && pulsatility == 1: last_time_fired = time, Jhyd = piecewise((1 - (phase - fracSysUp)/fracSysDown)*VhydAmp_test, phase > fracSysUp && phase <= 1 - fracDia, phase/fracSysUp*VhydAmp_test, phase <= fracSysUp, 0, phase >= 1 - fracDia, Jhyd); pulsatile_basis: at 0 after time < time_Jhyd_step && time - last_time_fired >= stepsize && pulsatility == 1: last_time_fired = time, Jhyd = piecewise(0, phase <= fracDia, (phase - fracDia)/fracSysDown*VhydAmp_basis, phase > fracDia && phase <= 1 - fracSysUp, ((1 - phase)*VhydAmp_basis)/fracSysUp, phase > 1 - fracSysUp, Jhyd); nonpulsatile_step: at 0 after time >= time_Jhyd_step: tmito_factor = 1, heartrate_bpm = heartrate_test, Jhyd = piecewise(Jhyd_test, pulsatility == 0, Jhyd); // Species initializations: ADPi = 39; ADPi has micromole_per_litre; ATPi = 5626; ATPi has micromole_per_litre; Cri = 9789; Cri has micromole_per_litre; PCri = 5711; PCri has micromole_per_litre; PCr = 5710; PCr has micromole_per_litre; ADP = 64; ADP has micromole_per_litre; ATP = 5601; ATP has micromole_per_litre; Cr = 9789; Cr has micromole_per_litre; P_ii = 910; P_ii has micromole_per_litre; P_i = 912; P_i has micromole_per_litre; // Compartment initializations: IMS = 0.0625; CYT = 0.75; cell = 1; // Variable initializations: time_Jhyd_step = 40; time_Jhyd_step has second; last_time_fired = 0; last_time_fired has second; stepsize = 0.001; stepsize has second; pulsatility = 1; Jhyd = 486.5; Jhyd has micromole_per_litre_per_second; fracSysUp = 0.1666666666; fracSysDown = 0.1666666666; VhydAmp_test has micromole_per_litre_per_second; VhydAmp_basis has micromole_per_litre_per_second; Jhyd_test = 627.6; Jhyd_test has micromole_per_litre_per_second; heartrate_bpm = 135; heartrate_bpm has unitDefinition_0000004; heartrate_test = 220; heartrate_test has unitDefinition_0000004; tmito_factor = 0; j_diff_pcr has micromole_per_litre_per_second; PSmomPCr = 155; PSmomPCr has per_second; j_diff_atp has micromole_per_litre_per_second; PSmomATP = 13.29477; PSmomATP has per_second; Kadp = 25; Kadp has micromole_per_litre; Kpi = 800; Kpi has micromole_per_litre; tmito = 0; tmito has second; jsyn has micromole_per_litre_per_second; Jhyd_basis = 486.5; Jhyd_basis has micromole_per_litre_per_second; Vmaxsyn = 1503.74; Vmaxsyn has micromole_per_litre_per_second; j_ck_mi has micromole_per_litre_per_second; VmaxMif has micromole_per_litre_per_second; KiaMi = 750; KiaMi has micromole_per_litre; KbMi = 5200; KbMi has micromole_per_litre; VmaxMib has micromole_per_litre_per_second; KicMi = 204.8; KicMi has micromole_per_litre; KdMi = 500; KdMi has micromole_per_litre; KibMi = 28800; KibMi has micromole_per_litre; KidMi = 1600; KidMi has micromole_per_litre; j_ck_mm has micromole_per_litre_per_second; VmaxMMf has micromole_per_litre_per_second; KiaMM = 900; KiaMM has micromole_per_litre; KbMM = 15500; KbMM has micromole_per_litre; VmaxMMb has micromole_per_litre_per_second; KicMM = 222.4; KicMM has micromole_per_litre; KdMM = 1670; KdMM has micromole_per_litre; KibMM = 34900; KibMM has micromole_per_litre; KidMM = 4730; KidMM has micromole_per_litre; j_diff_adp has micromole_per_litre_per_second; j_diff_cr has micromole_per_litre_per_second; PSmomCr = 155; PSmomCr has per_second; j_diff_pi has micromole_per_litre_per_second; PSmomPi = 194; PSmomPi has per_second; heartrate_basis = 135; heartrate_basis has unitDefinition_0000004; ck_factor_iaa = 1; ck_factor_ia = 0.0286; K_CK_eq = 152; VmaxMif_full_activity = 882.0756; VmaxMif_full_activity has micromole_per_litre_per_second; VmaxMMf_full_activity = 11441.78; VmaxMMf_full_activity has micromole_per_litre_per_second; // Other declarations: var last_time_fired, pulsatility, Jhyd, phase, VhydAmp_test, fracDia, VhydAmp_basis; var Jhyd_test, heartrate_bpm, tmito_factor, j_diff_pcr, j_diff_atp, densyn; var tmito, vatpnorm, jsyn, r_diff_pcr, j_ck_mi, VmaxMif, VmaxMib, j_ck_mm; var VmaxMMf, VmaxMMb, j_diff_adp, j_diff_cr, j_diff_pi; const IMS, CYT, cell, time_Jhyd_step, stepsize, fracSysUp, fracSysDown; const heartrate_test, PSmomPCr, PSmomATP, Kadp, Kpi, Jhyd_basis, Vmaxsyn; const KiaMi, KbMi, KicMi, KdMi, KibMi, KidMi, KiaMM, KbMM, KicMM, KdMM; const KibMM, KidMM, PSmomCr, PSmomPi, heartrate_basis, ck_factor_iaa, ck_factor_ia; const K_CK_eq, VmaxMif_full_activity, VmaxMMf_full_activity; // Unit definitions: unit micromole = 1e-6 mole; unit micromole_per_litre = 1e-6 mole / litre; unit micromole_per_litre_per_second = 1e-6 mole / (litre * second); unit unitDefinition_0000004 = 1 / 60 second; unit per_second = 1 / second; // Display Names: unitDefinition_0000004 is "per_minute"; end