C C There are a total of 21 entries in the algebraic variable array. C There are a total of 20 entries in each of the rate and state variable arrays. C There are a total of 50 entries in the constant variable array. C C C VOI is time in component environment (second). C ALGBRC(6) is LRG in component beta_adrenergic_receptor_module (micromolar). C ALGBRC(8) is RG in component beta_adrenergic_receptor_module (micromolar). C ALGBRC(1) is LR in component beta_adrenergic_receptor_module (micromolar). C STATES(1) is beta1_AR in component beta_adrenergic_receptor_module (micromolar). C STATES(2) is Gs in component beta_adrenergic_receptor_module (micromolar). C STATES(3) is beta1_ARact in component beta_adrenergic_receptor_module (micromolar). C STATES(4) is beta1_AR_S464 in component beta_adrenergic_receptor_module (micromolar). C STATES(5) is beta1_AR_S301 in component beta_adrenergic_receptor_module (micromolar). C STATES(6) is L in component beta_adrenergic_receptor_module (micromolar). C CONSTS(1) is Ltotmax in component beta_adrenergic_receptor_module (micromolar). C CONSTS(2) is KL in component beta_adrenergic_receptor_module (micromolar). C CONSTS(3) is KR in component beta_adrenergic_receptor_module (micromolar). C CONSTS(4) is KC in component beta_adrenergic_receptor_module (micromolar). C CONSTS(5) is Gstot in component beta_adrenergic_receptor_module (micromolar). C CONSTS(6) is k_betaARK_plus in component beta_adrenergic_receptor_module (first_order_rate_constant). C CONSTS(7) is k_betaARK_minus in component beta_adrenergic_receptor_module (first_order_rate_constant). C CONSTS(8) is k_PKA_plus in component beta_adrenergic_receptor_module (second_order_rate_constant). C CONSTS(9) is k_PKA_minus in component beta_adrenergic_receptor_module (first_order_rate_constant). C STATES(7) is Gs_beta_gamma in component Gs_activation_module (micromolar). C ALGBRC(10) is PKACI in component PKA_activation_module (micromolar). C STATES(8) is Gs_alpha_GTPtot in component Gs_activation_module (micromolar). C STATES(9) is Gs_alpha_GDP in component Gs_activation_module (micromolar). C CONSTS(10) is k_gact in component Gs_activation_module (first_order_rate_constant). C CONSTS(11) is k_hyd in component Gs_activation_module (first_order_rate_constant). C CONSTS(12) is k_reassoc in component Gs_activation_module (second_order_rate_constant). C STATES(10) is cAMPtot in component cyclic_AMP_metabolism_module (micromolar). C STATES(11) is AC in component cyclic_AMP_metabolism_module (micromolar). C STATES(12) is Gs_alpha_GTP in component cyclic_AMP_metabolism_module (micromolar). C ALGBRC(3) is Gs_alpha_GTP_AC in component cyclic_AMP_metabolism_module (micromolar). C STATES(13) is PDE in component cyclic_AMP_metabolism_module (micromolar). C CONSTS(13) is ACtot in component cyclic_AMP_metabolism_module (micromolar). C CONSTS(14) is ATP in component cyclic_AMP_metabolism_module (micromolar). C CONSTS(15) is PDEtot in component cyclic_AMP_metabolism_module (micromolar). C ALGBRC(2) is PDEinhib in component cyclic_AMP_metabolism_module (micromolar). C CONSTS(16) is IBMXtot in component cyclic_AMP_metabolism_module (micromolar). C STATES(14) is IBMX in component cyclic_AMP_metabolism_module (micromolar). C CONSTS(17) is fsktot in component cyclic_AMP_metabolism_module (micromolar). C STATES(15) is fsk in component cyclic_AMP_metabolism_module (micromolar). C ALGBRC(7) is fsk_AC in component cyclic_AMP_metabolism_module (micromolar). C CONSTS(18) is kAC_basal in component cyclic_AMP_metabolism_module (first_order_rate_constant). C CONSTS(19) is kAC_fsk in component cyclic_AMP_metabolism_module (first_order_rate_constant). C CONSTS(20) is k_PDE in component cyclic_AMP_metabolism_module (first_order_rate_constant). C CONSTS(21) is kAC_Gs_alpha in component cyclic_AMP_metabolism_module (first_order_rate_constant). C CONSTS(22) is Km_basal in component cyclic_AMP_metabolism_module (micromolar). C CONSTS(23) is Km_PDE in component cyclic_AMP_metabolism_module (micromolar). C CONSTS(24) is Km_fsk in component cyclic_AMP_metabolism_module (micromolar). C CONSTS(25) is K_fsk in component cyclic_AMP_metabolism_module (micromolar). C CONSTS(26) is Km_Gs_alpha_GTP in component cyclic_AMP_metabolism_module (micromolar). C CONSTS(27) is K_Gs_alpha in component cyclic_AMP_metabolism_module (micromolar). C CONSTS(28) is K_IBMX in component cyclic_AMP_metabolism_module (micromolar). C ALGBRC(11) is cAMP in component PKA_activation_module (micromolar). C ALGBRC(12) is PKACII in component PKA_activation_module (micromolar). C ALGBRC(13) is PKAtemp in component PKA_activation_module (micromolar). C ALGBRC(14) is ARCI in component PKA_activation_module (micromolar). C ALGBRC(15) is A2RCI in component PKA_activation_module (micromolar). C ALGBRC(16) is A2RI in component PKA_activation_module (micromolar). C ALGBRC(17) is A2RCII in component PKA_activation_module (micromolar). C ALGBRC(18) is A2RII in component PKA_activation_module (micromolar). C ALGBRC(19) is ARCII in component PKA_activation_module (micromolar). C CONSTS(29) is Ki_pki in component PKA_activation_module (micromolar). C CONSTS(30) is PKAItot in component PKA_activation_module (micromolar). C CONSTS(31) is PKAIItot in component PKA_activation_module (micromolar). C CONSTS(32) is PKItot in component PKA_activation_module (micromolar). C CONSTS(33) is KA in component PKA_activation_module (micromolar). C CONSTS(34) is KB in component PKA_activation_module (micromolar). C CONSTS(35) is KD in component PKA_activation_module (micromolar). C CONSTS(36) is KPKI in component PKA_activation_module (micromolar). C ALGBRC(20) is PKI in component PKA_activation_module (micromolar). C ALGBRC(4) is fracPLBp in component phospholamban_regulation_module (dimensionless). C ALGBRC(21) is fracPLB in component phospholamban_regulation_module (dimensionless). C CONSTS(37) is fracPLBo in component phospholamban_regulation_module (dimensionless). C STATES(16) is PLBp in component phospholamban_regulation_module (micromolar). C ALGBRC(9) is PLB in component phospholamban_regulation_module (micromolar). C STATES(17) is Inhib1ptot in component phospholamban_regulation_module (micromolar). C STATES(18) is Inhib1 in component phospholamban_regulation_module (micromolar). C STATES(19) is Inhib1p in component phospholamban_regulation_module (micromolar). C ALGBRC(5) is PP1_Inhib1p in component phospholamban_regulation_module (micromolar). C STATES(20) is PP1 in component phospholamban_regulation_module (micromolar). C CONSTS(38) is PP1tot in component phospholamban_regulation_module (micromolar). C CONSTS(39) is PLBtot in component phospholamban_regulation_module (micromolar). C CONSTS(40) is Inhib1tot in component phospholamban_regulation_module (micromolar). C CONSTS(41) is epsilon in component phospholamban_regulation_module (dimensionless). C CONSTS(42) is kPKA_PLB in component phospholamban_regulation_module (first_order_rate_constant). C CONSTS(43) is KmPKA_PLB in component phospholamban_regulation_module (micromolar). C CONSTS(44) is kPKA_Inhib1 in component phospholamban_regulation_module (first_order_rate_constant). C CONSTS(45) is kPP1_PLB in component phospholamban_regulation_module (first_order_rate_constant). C CONSTS(46) is KmPP1_PLB in component phospholamban_regulation_module (micromolar). C CONSTS(47) is KmPKA_Inhib1 in component phospholamban_regulation_module (micromolar). C CONSTS(48) is VmaxPP2A_Inhib1 in component phospholamban_regulation_module (flux). C CONSTS(49) is KmPP2A_Inhib1 in component phospholamban_regulation_module (micromolar). C CONSTS(50) is KInhib1 in component phospholamban_regulation_module (micromolar). C RATES(6) is d/dt L in component beta_adrenergic_receptor_module (micromolar). C RATES(2) is d/dt Gs in component beta_adrenergic_receptor_module (micromolar). C RATES(1) is d/dt beta1_AR in component beta_adrenergic_receptor_module (micromolar). C RATES(3) is d/dt beta1_ARact in component beta_adrenergic_receptor_module (micromolar). C RATES(4) is d/dt beta1_AR_S464 in component beta_adrenergic_receptor_module (micromolar). C RATES(5) is d/dt beta1_AR_S301 in component beta_adrenergic_receptor_module (micromolar). C RATES(8) is d/dt Gs_alpha_GTPtot in component Gs_activation_module (micromolar). C RATES(7) is d/dt Gs_beta_gamma in component Gs_activation_module (micromolar). C RATES(9) is d/dt Gs_alpha_GDP in component Gs_activation_module (micromolar). C RATES(12) is d/dt Gs_alpha_GTP in component cyclic_AMP_metabolism_module (micromolar). C RATES(15) is d/dt fsk in component cyclic_AMP_metabolism_module (micromolar). C RATES(11) is d/dt AC in component cyclic_AMP_metabolism_module (micromolar). C RATES(13) is d/dt PDE in component cyclic_AMP_metabolism_module (micromolar). C RATES(14) is d/dt IBMX in component cyclic_AMP_metabolism_module (micromolar). C RATES(10) is d/dt cAMPtot in component cyclic_AMP_metabolism_module (micromolar). C RATES(20) is d/dt PP1 in component phospholamban_regulation_module (micromolar). C RATES(19) is d/dt Inhib1p in component phospholamban_regulation_module (micromolar). C RATES(16) is d/dt PLBp in component phospholamban_regulation_module (micromolar). C RATES(17) is d/dt Inhib1ptot in component phospholamban_regulation_module (micromolar). C RATES(18) is d/dt Inhib1 in component phospholamban_regulation_module (micromolar). C SUBROUTINE initConsts(CONSTS, RATES, STATES) REAL CONSTS(*), RATES(*), STATES(*) STATES(1) = 0.0001 STATES(2) = 3.182 STATES(3) = 0.01205 STATES(4) = 0 STATES(5) = 1.154e-3 STATES(6) = 0.988 CONSTS(1) = 1 CONSTS(2) = 0.285 CONSTS(3) = 0.062 CONSTS(4) = 33 CONSTS(5) = 3.83 CONSTS(6) = 1.1e-3 CONSTS(7) = 2.2e-3 CONSTS(8) = 3.6e-3 CONSTS(9) = 2.2e-3 STATES(7) = 0.02569 STATES(8) = 0.02505 STATES(9) = 6.44e-4 CONSTS(10) = 16 CONSTS(11) = 0.8 CONSTS(12) = 1.21e3 STATES(10) = 0.8453 STATES(11) = 0.04706295 STATES(12) = 0.02241295 STATES(13) = 0.0389 CONSTS(13) = 49.7e-3 CONSTS(14) = 5e3 CONSTS(15) = 38.9e-3 CONSTS(16) = 0 STATES(14) = 0 CONSTS(17) = 0 STATES(15) = 0 CONSTS(18) = 0.2 CONSTS(19) = 7.3 CONSTS(20) = 5 CONSTS(21) = 8.5 CONSTS(22) = 1.03e3 CONSTS(23) = 1.3 CONSTS(24) = 860 CONSTS(25) = 44 CONSTS(26) = 0.4 CONSTS(27) = 0.4 CONSTS(28) = 30 CONSTS(29) = 0.2e-3 CONSTS(30) = 0.59 CONSTS(31) = 0.025 CONSTS(32) = 0.18 CONSTS(33) = 9.14e-3 CONSTS(34) = 1.64e-3 CONSTS(35) = 4.375e-3 CONSTS(36) = 2e-4 CONSTS(37) = 0.9613 STATES(16) = 4.105 STATES(17) = 0.0526 STATES(18) = 0.2474 STATES(19) = 6.27339e-5 STATES(20) = 0.8374627 CONSTS(38) = 0.89 CONSTS(39) = 106 CONSTS(40) = 0.3 CONSTS(41) = 10 CONSTS(42) = 54 CONSTS(43) = 21 CONSTS(44) = 60 CONSTS(45) = 8.5 CONSTS(46) = 7 CONSTS(47) = 1 CONSTS(48) = 14 CONSTS(49) = 1 CONSTS(50) = 1e-3 RETURN END SUBROUTINE computeRates(VOI, CONSTS, RATES, STATES, ALGBRC) REAL VOI, CONSTS(*), RATES(*), STATES(*), ALGBRC(*) RATES(9) = CONSTS(11)*STATES(8) - CONSTS(12)*STATES(9)*STATES(7) ALGBRC(3) = ( STATES(12)*STATES(11))/CONSTS(27) RATES(12) = STATES(8) - (ALGBRC(3)+STATES(12)) RATES(11) = CONSTS(13) - (ALGBRC(3)+STATES(11)) ALGBRC(2) = ( STATES(13)*STATES(14))/CONSTS(28) RATES(13) = CONSTS(15) - (ALGBRC(2)+STATES(13)) RATES(14) = CONSTS(16) - (ALGBRC(2)+STATES(14)) ALGBRC(5) = ( STATES(20)*STATES(19))/CONSTS(50) RATES(20) = CONSTS(38) - (ALGBRC(5)+STATES(20)) RATES(19) = STATES(17) - (ALGBRC(5)+STATES(19)) ALGBRC(6) = ( STATES(6)*STATES(1)*STATES(2))/( CONSTS(2)*CONSTS(3)) ALGBRC(1) = ( STATES(6)*STATES(1))/CONSTS(2) RATES(6) = CONSTS(1) - (ALGBRC(1)+ALGBRC(6)+STATES(6)) RATES(4) = CONSTS(6)*(ALGBRC(1)+ALGBRC(6)) - CONSTS(7)*STATES(4) ALGBRC(7) = ( STATES(15)*STATES(11))/CONSTS(25) RATES(15) = CONSTS(17) - (ALGBRC(7)+STATES(15)) RATES(10) = (( CONSTS(18)*STATES(11)*CONSTS(14))/(CONSTS(22)+CONSTS(14))+( CONSTS(21)*ALGBRC(3)*CONSTS(14))/(CONSTS(26)+CONSTS(14))+( CONSTS(19)*ALGBRC(7)*CONSTS(14))/(CONSTS(24)+CONSTS(14))) - ( CONSTS(20)*STATES(13)*STATES(10))/(CONSTS(23)+STATES(10)) ALGBRC(8) = ( STATES(1)*STATES(2))/CONSTS(4) RATES(2) = CONSTS(5) - (ALGBRC(8)+ALGBRC(6)+STATES(2)) RATES(1) = STATES(3) - (ALGBRC(1)+ALGBRC(6)+ALGBRC(8)+STATES(1)) RATES(8) = CONSTS(10)*(ALGBRC(8)+ALGBRC(6)) - CONSTS(11)*STATES(8) RATES(7) = CONSTS(10)*(ALGBRC(8)+ALGBRC(6)) - CONSTS(12)*STATES(9)*STATES(7) CALL minimize(minfunc_0, CONSTS, VARIABLES, ) RATES(3) = ( CONSTS(7)*STATES(4) - CONSTS(6)*(ALGBRC(1)+ALGBRC(6)))+( CONSTS(9)*STATES(5) - CONSTS(8)*ALGBRC(10)*STATES(3)) RATES(5) = CONSTS(8)*ALGBRC(10)*STATES(3) - CONSTS(9)*STATES(5) ALGBRC(9) = CONSTS(39) - STATES(16) RATES(16) = ( CONSTS(42)*ALGBRC(10)*ALGBRC(9))/(CONSTS(43)+ALGBRC(9)) - ( CONSTS(45)*STATES(20)*STATES(16))/(CONSTS(46)+STATES(16)) RATES(17) = ( CONSTS(44)*ALGBRC(10)*STATES(17))/(CONSTS(47)+STATES(17)) - ( CONSTS(48)*STATES(18))/(CONSTS(49)+STATES(18)) RATES(18) = ( CONSTS(48)*STATES(18))/(CONSTS(49)+STATES(18)) - ( CONSTS(44)*ALGBRC(10)*STATES(17))/(CONSTS(47)+STATES(17)) RETURN END SUBROUTINE computeVariables(VOI, CONSTS, RATES, STATES, ALGBRC) REAL VOI, CONSTS(*), RATES(*), STATES(*), ALGBRC(*) ALGBRC(3) = ( STATES(12)*STATES(11))/CONSTS(27) ALGBRC(2) = ( STATES(13)*STATES(14))/CONSTS(28) ALGBRC(5) = ( STATES(20)*STATES(19))/CONSTS(50) ALGBRC(6) = ( STATES(6)*STATES(1)*STATES(2))/( CONSTS(2)*CONSTS(3)) ALGBRC(1) = ( STATES(6)*STATES(1))/CONSTS(2) ALGBRC(7) = ( STATES(15)*STATES(11))/CONSTS(25) ALGBRC(8) = ( STATES(1)*STATES(2))/CONSTS(4) ALGBRC(9) = CONSTS(39) - STATES(16) ALGBRC(4) = STATES(16)/CONSTS(39) ALGBRC(21) = ALGBRC(9)/CONSTS(39) RETURN END REAL FUNCTION minfunc_0(CONSTS, VARIABLES) REAL CONSTS(*), VARIABLES(*) minfunc_0[1] = abs(ALGBRC(20) - ( CONSTS(32)*CONSTS(29))/(CONSTS(29)+ALGBRC(10)+ALGBRC(12))) minfunc_0[2] = abs(ALGBRC(15) - (ALGBRC(10)/CONSTS(35))*ALGBRC(10)*(1.00000+ALGBRC(20)/CONSTS(29))) minfunc_0[3] = abs(ALGBRC(16) - ALGBRC(10)*(1.00000+ALGBRC(20)/CONSTS(29))) minfunc_0[4] = abs(ALGBRC(17) - (ALGBRC(12)/CONSTS(35))*ALGBRC(12)*(1.00000+ALGBRC(20)/CONSTS(29))) minfunc_0[5] = abs(ALGBRC(18) - ALGBRC(12)*(1.00000+ALGBRC(20)/CONSTS(29))) minfunc_0[6] = abs(ALGBRC(14) - (CONSTS(33)/ALGBRC(11))*ALGBRC(15)) minfunc_0[7] = abs(ALGBRC(19) - (CONSTS(33)/ALGBRC(11))*ALGBRC(17)) minfunc_0[8] = abs(ALGBRC(11) - ((STATES(10) - (ALGBRC(14)+ 2.00000*ALGBRC(15)+ 2.00000*ALGBRC(16))) - (ALGBRC(19)+ 2.00000*ALGBRC(17)+ 2.00000*ALGBRC(18)))) minfunc_0[9] = abs(ALGBRC(13) - (( CONSTS(33)*CONSTS(34))/CONSTS(35)+( CONSTS(33)*ALGBRC(11))/CONSTS(35)+( ALGBRC(11)*ALGBRC(11))/CONSTS(35))) minfunc_0[10] = abs(ALGBRC(10) - ( 2.00000*CONSTS(30)*ALGBRC(11)*ALGBRC(11) - ALGBRC(10)*(1.00000+ALGBRC(20)/CONSTS(29))*( ALGBRC(13)*ALGBRC(10)+ ALGBRC(11)*ALGBRC(11)))) minfunc_0[11] = abs(ALGBRC(12) - ( 2.00000*CONSTS(31)*ALGBRC(11)*ALGBRC(11) - ALGBRC(12)*(1.00000+ALGBRC(20)/CONSTS(29))*( ALGBRC(13)*ALGBRC(12)+ ALGBRC(11)*ALGBRC(11)))) RETURN END