0.2 file:/Users/Brian/Desktop/Kapela_VSM.mod Electrical conductance http://bhi.washington.edu/OPB#OPB_00015 Temperature http://bhi.washington.edu/OPB#OPB_00293 Charge flow rate http://bhi.washington.edu/OPB#OPB_00318 Chemical concentration http://bhi.washington.edu/OPB#OPB_00340 Electrical capacitance http://bhi.washington.edu/OPB#OPB_00446 Electrical potential http://bhi.washington.edu/OPB#OPB_00506 Particle count http://bhi.washington.edu/OPB#OPB_01001 Surface area http://bhi.washington.edu/OPB#OPB_01043 Fluid volume http://bhi.washington.edu/OPB#OPB_01061 State fraction of chemical http://bhi.washington.edu/OPB#OPB_01298 Nernst potential http://bhi.washington.edu/OPB#OPB_01581 guanine http://purl.obolibrary.org/obo/CHEBI_16235 3',5'-cyclic GMP http://purl.obolibrary.org/obo/CHEBI_16356 nitric oxide http://purl.obolibrary.org/obo/CHEBI_16480 diglyceride http://purl.obolibrary.org/obo/CHEBI_18035 myo-inositol trisphosphate http://purl.obolibrary.org/obo/CHEBI_25450 sodium(1+) http://purl.obolibrary.org/obo/CHEBI_29101 potassium(1+) http://purl.obolibrary.org/obo/CHEBI_29103 calcium(2+) http://purl.obolibrary.org/obo/CHEBI_29108 chlorine(1+) http://purl.obolibrary.org/obo/CHEBI_30120 noradrenaline http://purl.obolibrary.org/obo/CHEBI_33569 phosphatidylinositol bisphosphate http://purl.obolibrary.org/obo/CHEBI_37328 voltage-gated potassium channel complex http://purl.obolibrary.org/obo/GO_0008076 calsequestrin-2 http://purl.obolibrary.org/obo/PR_000005057 calmodulin (human) http://purl.obolibrary.org/obo/PR_P62158 Vascular smooth muscle cell http://purl.org/sig/ont/fma/fma284560 Plasma membrane http://purl.org/sig/ont/fma/fma63841 Portion of cytosol http://purl.org/sig/ont/fma/fma66836 Matrix of endoplasmic reticulum cistern http://purl.org/sig/ont/fma/fma67120 Sarcoplasmic reticulum http://purl.org/sig/ont/fma/fma67225 Matrix of endoplasmic reticulum http://purl.org/sig/ont/fma/fma72448 Portion of extracellular matrix http://purl.org/sig/ont/fma/fma9672 A physical entity that is defined by linking multiple physical entity terms with structural relations. A mathematical and/or logical expression that determines the value of a data structure. An element of a SemSim model that relates to the mathematical or logical representation of physical quantities or qualities. A physical dependency defined in a specific SemSim model. A physical entity defined in a specific SemSim model. A physical process defined in a specific SemSim model. A physical property defined in a specific SemSim model. A computational element that stores numerical and/or logical information related to the model. A data structure whose value is limited to decimals. A data structure whose value is limited to the whole numbers. A data structure unique to JSim's Mathematical Modeling Language (MML) used to set one or more model input values at runtime. A quantitative relation between values of physical properties that occurs over a span of time and that determines the time-course of a physical process. A physics analytical entity that represents the material, energy, and/or information content of material or immaterial, space-occupying continuants. A SemSim model element used to represent, in whole or in part, the physical meaning of a computational element. A physical processural entity that is a flow, or the control of a flow, of energy and/or information amongst physical continuants that are participants in the physical process. A physical attribute of an instance of a physical entity, an occurrence of a physical process, or a physical dependency that has a quantitative value that is measurable by a physical device or method, or is computable from such values. A data structure whose value is limited to the real numbers. A physical dependency that is defined using a term in an external knowledge resource. A physical entity that is defined using a term from an external knowledge resource. A physical process that is defined using a term in an external knowledge resource. A physical property that is defined using a term in an external knowledge resource. A logical expression that constrains, but does not define, the value of a data structure. Example: x > 0. A computational or physical element of a SemSim model. A grouping of one or more data structures that comprise a computationally or physically distinct part of a model or submodel. A physical quantity chosen as a standard in terms of which other physical quantities may be expressed. cGMP production rate term <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <plus /> <apply> <times /> <apply> <plus /> <ci>k_m1sGC</ci> <ci>k_2sGC</ci> </apply> <ci>k_DsGC</ci> </apply> <apply> <times /> <ci>k_m1sGC</ci> <ci>k_m2sGC</ci> </apply> </apply> <apply> <times /> <ci>k_1sGC</ci> <ci>k_3sGC</ci> </apply> </apply> </math> A0_sGC = ((k_m1sGC+k_2sGC)*k_DsGC+k_m1sGC*k_m2sGC)/(k_1sGC*k_3sGC) cGMP production rate term <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <plus /> <apply> <times /> <apply> <plus /> <ci>k_1sGC</ci> <ci>k_3sGC</ci> </apply> <ci>k_DsGC</ci> </apply> <apply> <times /> <apply> <plus /> <ci>k_2sGC</ci> <ci>k_m2sGC</ci> </apply> <ci>k_1sGC</ci> </apply> </apply> <apply> <times /> <ci>k_1sGC</ci> <ci>k_3sGC</ci> </apply> </apply> </math> A1_sGC = ((k_1sGC+k_3sGC)*k_DsGC+(k_2sGC+k_m2sGC)*k_1sGC)/(k_1sGC*k_3sGC) Surface area of the smooth muscle cell <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <ci>C_m</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="picofarad/cm^2">1E6</cn> </apply> </math> A_m = C_m/1E6 Surface area http://bhi.washington.edu/OPB#OPB_01043 cGMP porduction rate NO sensitivity term <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <ci>k_2sGC</ci> <ci>k_3sGC</ci> </apply> </math> B5_sGC = k_2sGC/k_3sGC Concentration of other Ca buffers <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.1</cn> </math> Bbar_F = .1 guanine http://purl.obolibrary.org/obo/CHEBI_16235 3',5'-cyclic GMP http://purl.obolibrary.org/obo/CHEBI_16356 nitric oxide http://purl.obolibrary.org/obo/CHEBI_16480 diglyceride http://purl.obolibrary.org/obo/CHEBI_18035 myo-inositol trisphosphate http://purl.obolibrary.org/obo/CHEBI_25450 sodium(1+) http://purl.obolibrary.org/obo/CHEBI_29101 sodium(1+) http://purl.obolibrary.org/obo/CHEBI_29101 sodium(1+) http://purl.obolibrary.org/obo/CHEBI_29101 potassium(1+) http://purl.obolibrary.org/obo/CHEBI_29103 potassium(1+) http://purl.obolibrary.org/obo/CHEBI_29103 potassium(1+) http://purl.obolibrary.org/obo/CHEBI_29103 calcium(2+) http://purl.obolibrary.org/obo/CHEBI_29108 calcium(2+) http://purl.obolibrary.org/obo/CHEBI_29108 calcium(2+) http://purl.obolibrary.org/obo/CHEBI_29108 calcium(2+) http://purl.obolibrary.org/obo/CHEBI_29108 calcium(2+) http://purl.obolibrary.org/obo/CHEBI_29108 chlorine(1+) http://purl.obolibrary.org/obo/CHEBI_30120 chlorine(1+) http://purl.obolibrary.org/obo/CHEBI_30120 chlorine(1+) http://purl.obolibrary.org/obo/CHEBI_30120 noradrenaline http://purl.obolibrary.org/obo/CHEBI_33569 phosphatidylinositol bisphosphate http://purl.obolibrary.org/obo/CHEBI_37328 Average sarcoplasmic reticulum calsequestrin concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>15</cn> </math> CSQNbar = 15 Chemical concentration http://bhi.washington.edu/OPB#OPB_00340 Total membrane capacitance <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>25</cn> </math> C_m = 25 Electrical capacitance http://bhi.washington.edu/OPB#OPB_00446 Extracellular Ca concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>2</cn> </math> Ca_e = 2 Chemical concentration http://bhi.washington.edu/OPB#OPB_00340 Ca_i0 Intracellular calcium concentration false Rate of change of intracellular calcium concentration with time <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <apply> <divide /> <apply> <minus /> <apply> <minus /> <apply> <plus /> <ci>ICa_totm</ci> <ci>I_SERCA</ci> </apply> <ci>I_rel</ci> </apply> <ci>I_IP3</ci> </apply> <apply> <times /> <apply> <times /> <ci>z_Ca</ci> <ci>F</ci> </apply> <ci>Vol_Ca</ci> </apply> </apply> <apply> <plus /> <apply> <plus /> <cn>1</cn> <apply> <divide /> <apply> <times /> <ci>Sbar_CM</ci> <ci>K_dCM</ci> </apply> <apply> <power /> <apply> <plus /> <ci>K_dCM</ci> <ci>Ca_i</ci> </apply> <cn>2</cn> </apply> </apply> </apply> <apply> <divide /> <apply> <times /> <ci>Bbar_F</ci> <ci>K_dB</ci> </apply> <apply> <power /> <apply> <plus /> <ci>K_dB</ci> <ci>Ca_i</ci> </apply> <cn>2</cn> </apply> </apply> </apply> </apply> <cn>-1</cn> </apply> </math> Ca_i:time = (ICa_totm+I_SERCA-I_rel-I_IP3)/(z_Ca*F*Vol_Ca)/(1+Sbar_CM*K_dCM/(K_dCM+Ca_i)^2+Bbar_F*K_dB/(K_dB+Ca_i)^2)*(-1) Initial intracellular calcium concentraion <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>6.8E-5</cn> </math> Ca_i0 = 6.8E-5 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <apply> <divide /> <apply> <minus /> <apply> <minus /> <apply> <plus /> <ci>ICa_totm</ci> <ci>I_SERCA</ci> </apply> <ci>I_rel</ci> </apply> <ci>I_IP3</ci> </apply> <apply> <times /> <apply> <times /> <ci>z_Ca</ci> <ci>F</ci> </apply> <ci>Vol_Ca</ci> </apply> </apply> <apply> <plus /> <apply> <plus /> <cn>1</cn> <apply> <divide /> <apply> <times /> <ci>Sbar_CM</ci> <ci>K_dCM</ci> </apply> <apply> <power /> <apply> <plus /> <ci>K_dCM</ci> <ci>Ca_i</ci> </apply> <cn>2</cn> </apply> </apply> </apply> <apply> <divide /> <apply> <times /> <ci>Bbar_F</ci> <ci>K_dB</ci> </apply> <apply> <power /> <apply> <plus /> <ci>K_dB</ci> <ci>Ca_i</ci> </apply> <cn>2</cn> </apply> </apply> </apply> </apply> <cn>-1</cn> </apply> </math> Ca_i:time = (ICa_totm+I_SERCA-I_rel-I_IP3)/(z_Ca*F*Vol_Ca)/(1+Sbar_CM*K_dCM/(K_dCM+Ca_i)^2+Bbar_F*K_dB/(K_dB+Ca_i)^2)*(-1) Chemical concentration http://bhi.washington.edu/OPB#OPB_00340 Ca_r0 Sarcoplasmic reticulum release space calcium concentration false Rate of change of sarcoplasmic reticulum release space calcium concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <divide /> <apply> <minus /> <ci>I_tr</ci> <ci>I_rel</ci> </apply> <apply> <times /> <apply> <times /> <ci>z_Ca</ci> <ci>F</ci> </apply> <ci>Vol_SRr</ci> </apply> </apply> <apply> <plus /> <cn>1</cn> <apply> <divide /> <apply> <times /> <ci>CSQNbar</ci> <ci>K_CSQN</ci> </apply> <apply> <power /> <apply> <plus /> <ci>K_CSQN</ci> <ci>Ca_r</ci> </apply> <cn>2</cn> </apply> </apply> </apply> </apply> </math> Ca_r:time = (I_tr-I_rel)/(z_Ca*F*Vol_SRr)/(1+CSQNbar*K_CSQN/(K_CSQN+Ca_r)^2) Intitial sarcoplasmic reticulum release space calcium concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.57</cn> </math> Ca_r0 = .57 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <divide /> <apply> <minus /> <ci>I_tr</ci> <ci>I_rel</ci> </apply> <apply> <times /> <apply> <times /> <ci>z_Ca</ci> <ci>F</ci> </apply> <ci>Vol_SRr</ci> </apply> </apply> <apply> <plus /> <cn>1</cn> <apply> <divide /> <apply> <times /> <ci>CSQNbar</ci> <ci>K_CSQN</ci> </apply> <apply> <power /> <apply> <plus /> <ci>K_CSQN</ci> <ci>Ca_r</ci> </apply> <cn>2</cn> </apply> </apply> </apply> </apply> </math> Ca_r:time = (I_tr-I_rel)/(z_Ca*F*Vol_SRr)/(1+CSQNbar*K_CSQN/(K_CSQN+Ca_r)^2) Chemical concentration http://bhi.washington.edu/OPB#OPB_00340 Ca_u0 Sarcoplasmic reticulum uptake space calcium concentration false Rate of change of sarcoplasmic reticulum uptake space calcium concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <apply> <minus /> <ci>I_SERCA</ci> <ci>I_tr</ci> </apply> <ci>I_IP3</ci> </apply> <apply> <times /> <apply> <times /> <ci>z_Ca</ci> <ci>F</ci> </apply> <ci>Vol_SRu</ci> </apply> </apply> </math> Ca_u:time = (I_SERCA-I_tr-I_IP3)/(z_Ca*F*Vol_SRu) Initial sarcoplasmic reticulum uptake space calcium concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.66</cn> </math> Ca_u0 = .66 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <apply> <minus /> <ci>I_SERCA</ci> <ci>I_tr</ci> </apply> <ci>I_IP3</ci> </apply> <apply> <times /> <apply> <times /> <ci>z_Ca</ci> <ci>F</ci> </apply> <ci>Vol_SRu</ci> </apply> </apply> </math> Ca_u:time = (I_SERCA-I_tr-I_IP3)/(z_Ca*F*Vol_SRu) Chemical concentration http://bhi.washington.edu/OPB#OPB_00340 Calcium activated chloride channel Calcium activated chloride channel current Calicum activated chloride channel current 1.0 1.0 Extracellular chloride concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>129</cn> </math> Cl_e = 129 Chemical concentration http://bhi.washington.edu/OPB#OPB_00340 Cl_i0 Intracellular chloride concentration false Rate of change of intracellular chloride concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <ci>ICl_totm</ci> <apply> <times /> <apply> <times /> <ci>z_Cl</ci> <ci>F</ci> </apply> <ci>Vol_i</ci> </apply> </apply> <cn>-1</cn> </apply> </math> Cl_i:time = ICl_totm/(z_Cl*F*Vol_i)*(-1) Initial intracellular chloride concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>59.4</cn> </math> Cl_i0 = 59.4 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <ci>ICl_totm</ci> <apply> <times /> <apply> <times /> <ci>z_Cl</ci> <ci>F</ci> </apply> <ci>Vol_i</ci> </apply> </apply> <cn>-1</cn> </apply> </math> Cl_i:time = ICl_totm/(z_Cl*F*Vol_i)*(-1) Chemical concentration http://bhi.washington.edu/OPB#OPB_00340 Diacylglycerol concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <ci>IP3</ci> </math> DAG = IP3 Chemical concentration http://bhi.washington.edu/OPB#OPB_00340 Nernst potential for calcium <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <cn>1</cn> <apply> <times /> <ci>z_Ca</ci> <ci>FRT</ci> </apply> </apply> <apply> <log /> <apply> <divide /> <ci>Ca_e</ci> <ci>Ca_i</ci> </apply> </apply> </apply> </math> E_Ca = 1/(z_Ca*FRT)*log(Ca_e/Ca_i) Nernst potential http://bhi.washington.edu/OPB#OPB_01581 Nernst potential for chloride <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <cn>1</cn> <apply> <times /> <ci>z_Cl</ci> <ci>FRT</ci> </apply> </apply> <apply> <log /> <apply> <divide /> <ci>Cl_e</ci> <ci>Cl_i</ci> </apply> </apply> </apply> </math> E_Cl = 1/(z_Cl*FRT)*log(Cl_e/Cl_i) Nernst potential http://bhi.washington.edu/OPB#OPB_01581 Nernst potential for potassium <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <cn>1</cn> <apply> <times /> <ci>z_K</ci> <ci>FRT</ci> </apply> </apply> <apply> <log /> <apply> <divide /> <ci>K_e</ci> <ci>K_i</ci> </apply> </apply> </apply> </math> E_K = 1/(z_K*FRT)*log(K_e/K_i) Nernst potential http://bhi.washington.edu/OPB#OPB_01581 Nernst potential for sodium <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <cn>1</cn> <apply> <times /> <ci>z_Na</ci> <ci>FRT</ci> </apply> </apply> <apply> <log /> <apply> <divide /> <ci>Na_e</ci> <ci>Na_i</ci> </apply> </apply> </apply> </math> E_Na = 1/(z_Na*FRT)*log(Na_e/Na_i) Nernst potential http://bhi.washington.edu/OPB#OPB_01581 Faraday constant http://bhi.washington.edu/OPB#OPB_00089 Faraday constant F over RT coefficient <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <ci>F</ci> <ci>RT</ci> </apply> </math> FRT = F/RT <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>96485.3399</cn> </math> F = 96485.3399 G_0 Number of active G proteins false Rate of change of number of active G proteins <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <minus /> <apply> <times /> <apply> <times /> <ci>k_aG</ci> <apply> <plus /> <ci>deltaG_0</ci> <ci>rho_rG</ci> </apply> </apply> <apply> <minus /> <ci>G_TG</ci> <ci>G</ci> </apply> </apply> <apply> <times /> <ci>k_dG</ci> <ci>G</ci> </apply> </apply> </math> G:time = k_aG*(deltaG_0+rho_rG)*(G_TG-G)-k_dG*G voltage-gated potassium channel complex http://purl.obolibrary.org/obo/GO_0008076 Initial number of active G proteins <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <apply> <times /> <ci>r_hG0</ci> <apply> <plus /> <ci>K_cG</ci> <ci>Ca_i0</ci> </apply> </apply> <apply> <times /> <ci>alpha_G</ci> <ci>Ca_i0</ci> </apply> </apply> <cn>1E-15</cn> </apply> </math> G_0 = r_hG0*(K_cG+Ca_i0)/(alpha_G*Ca_i0)*1E-15 Total number of G proteins <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1E5</cn> </math> G_TG = 1E5 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <minus /> <apply> <times /> <apply> <times /> <ci>k_aG</ci> <apply> <plus /> <ci>deltaG_0</ci> <ci>rho_rG</ci> </apply> </apply> <apply> <minus /> <ci>G_TG</ci> <ci>G</ci> </apply> </apply> <apply> <times /> <ci>k_dG</ci> <ci>G</ci> </apply> </apply> </math> G:time = k_aG*(deltaG_0+rho_rG)*(G_TG-G)-k_dG*G Particle count http://bhi.washington.edu/OPB#OPB_01001 Total cell nonselective cation channel calcium current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <ci>A_m</ci> <ci>d_NSCmin</ci> </apply> <ci>Po_NSC</ci> </apply> <ci>PCa_NSC</ci> </apply> <ci>V_m</ci> </apply> <apply> <power /> <ci>z_Ca</ci> <cn>2</cn> </apply> </apply> <ci>F</ci> </apply> <ci>FRT</ci> </apply> <apply> <minus /> <ci>Ca_e</ci> <apply> <times /> <ci>Ca_i</ci> <apply> <exp /> <apply> <times /> <apply> <times /> <ci>z_Ca</ci> <ci>V_m</ci> </apply> <ci>FRT</ci> </apply> </apply> </apply> </apply> </apply> <apply> <minus /> <cn>1</cn> <apply> <exp /> <apply> <times /> <apply> <times /> <ci>z_Ca</ci> <ci>V_m</ci> </apply> <ci>FRT</ci> </apply> </apply> </apply> </apply> <cn>1E6</cn> </apply> </math> ICa_NSC = A_m*d_NSCmin*Po_NSC*PCa_NSC*V_m*z_Ca^2*F*FRT*(Ca_e-Ca_i*exp(z_Ca*V_m*FRT))/(1-exp(z_Ca*V_m*FRT))*1000000.0000000003 Charge flow rate http://bhi.washington.edu/OPB#OPB_00318 Total cell store operated cation channel maximal calcium current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <times /> <ci>gCa_SOC</ci> <ci>P_SOC</ci> </apply> <apply> <minus /> <ci>V_m</ci> <ci>E_Ca</ci> </apply> </apply> </math> ICa_SOC = gCa_SOC*P_SOC*(V_m-E_Ca) Total cell plasma membrane calcium current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <plus /> <apply> <plus /> <apply> <minus /> <apply> <plus /> <ci>ICa_SOC</ci> <ci>I_VOCC</ci> </apply> <apply> <times /> <ci>I_NCX</ci> <cn>2</cn> </apply> </apply> <ci>I_PMCA</ci> </apply> <ci>ICa_NSC</ci> </apply> </math> ICa_totm = ICa_SOC+I_VOCC-I_NCX*2+I_PMCA+ICa_NSC Total cell sodium/potassium/chloride cotransporter chloride current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <ci>R_NaKClcGMP</ci> <ci>z_Cl</ci> </apply> <ci>A_m</ci> </apply> <ci>L_NaKCl</ci> </apply> <ci>F</ci> </apply> <ci>RT</ci> </apply> <apply> <log /> <apply> <times /> <apply> <times /> <apply> <divide /> <ci>Na_e</ci> <ci>Na_i</ci> </apply> <apply> <divide /> <ci>K_e</ci> <ci>K_i</ci> </apply> </apply> <apply> <power /> <apply> <divide /> <ci>Cl_e</ci> <ci>Cl_i</ci> </apply> <cn>2</cn> </apply> </apply> </apply> </apply> <cn>-1E9</cn> </apply> </math> ICl_NaKCl = R_NaKClcGMP*z_Cl*A_m*L_NaKCl*F*RT*log(Na_e/Na_i*(K_e/K_i)*(Cl_e/Cl_i)^2)*(-9.999999999999999E8) Total cell plasma membrane chloride current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <plus /> <ci>ICl_NaKCl</ci> <ci>I_ClCa</ci> </apply> </math> ICl_totm = ICl_NaKCl+I_ClCa Total cell nonselective cation channel maximal potassium current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <ci>A_m</ci> <apply> <plus /> <apply> <divide /> <ci>DAG</ci> <apply> <plus /> <ci>DAG</ci> <ci>K_NSC</ci> </apply> </apply> <ci>d_NSCmin</ci> </apply> </apply> <ci>Po_NSC</ci> </apply> <ci>PK_NSC</ci> </apply> <ci>V_m</ci> </apply> <ci>F</ci> </apply> <ci>FRT</ci> </apply> <apply> <minus /> <ci>K_e</ci> <apply> <times /> <ci>K_i</ci> <apply> <exp /> <apply> <times /> <ci>V_m</ci> <ci>FRT</ci> </apply> </apply> </apply> </apply> </apply> <apply> <minus /> <cn>1</cn> <apply> <exp /> <apply> <times /> <ci>V_m</ci> <ci>FRT</ci> </apply> </apply> </apply> </apply> <cn>1E6</cn> </apply> </math> IK_NSC = A_m*(DAG/(DAG+K_NSC)+d_NSCmin)*Po_NSC*PK_NSC*V_m*F*FRT*(K_e-K_i*exp(V_m*FRT))/(1-exp(V_m*FRT))*1000000.0000000003 Total cell sodium/potassium/chloride cotransporter potassium current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <ci>ICl_NaKCl</ci> <cn>-0.5</cn> </apply> </math> IK_NaKCl = ICl_NaKCl*(-0.5) Total cell plasma membrane potassium current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <minus /> <apply> <plus /> <apply> <plus /> <apply> <plus /> <apply> <plus /> <ci>IK_NaKCl</ci> <ci>I_BKCa</ci> </apply> <ci>I_Kv</ci> </apply> <ci>IK_NSC</ci> </apply> <ci>I_Kleak</ci> </apply> <apply> <times /> <ci>I_NaK</ci> <cn>2</cn> </apply> </apply> </math> IK_totm = IK_NaKCl+I_BKCa+I_Kv+IK_NSC+I_Kleak-I_NaK*2 Total cell nonselective cation channel maximal sodium current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <ci>A_m</ci> <apply> <plus /> <apply> <divide /> <ci>DAG</ci> <apply> <plus /> <ci>DAG</ci> <ci>K_NSC</ci> </apply> </apply> <ci>d_NSCmin</ci> </apply> </apply> <ci>Po_NSC</ci> </apply> <ci>PNa_NSC</ci> </apply> <ci>V_m</ci> </apply> <ci>F</ci> </apply> <ci>FRT</ci> </apply> <apply> <minus /> <ci>Na_e</ci> <apply> <times /> <ci>Na_i</ci> <apply> <exp /> <apply> <times /> <ci>V_m</ci> <ci>FRT</ci> </apply> </apply> </apply> </apply> </apply> <apply> <minus /> <cn>1</cn> <apply> <exp /> <apply> <times /> <ci>V_m</ci> <ci>FRT</ci> </apply> </apply> </apply> </apply> <cn>1E6</cn> </apply> </math> INa_NSC = A_m*(DAG/(DAG+K_NSC)+d_NSCmin)*Po_NSC*PNa_NSC*V_m*F*FRT*(Na_e-Na_i*exp(V_m*FRT))/(1-exp(V_m*FRT))*1000000.0000000003 Total cell sodium/potassium/chloride cotransporter sodium current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <ci>ICl_NaKCl</ci> <cn>-0.5</cn> </apply> </math> INa_NaKCl = ICl_NaKCl*(-0.5) Total cell store operated cation channel maximal sodium current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <times /> <ci>gNa_SOC</ci> <ci>P_SOC</ci> </apply> <apply> <minus /> <ci>V_m</ci> <ci>E_Na</ci> </apply> </apply> </math> INa_SOC = gNa_SOC*P_SOC*(V_m-E_Na) Total cell plasma membrane sodium current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <plus /> <apply> <plus /> <apply> <plus /> <apply> <plus /> <ci>INa_NaKCl</ci> <ci>INa_SOC</ci> </apply> <apply> <times /> <ci>I_NaK</ci> <cn>3</cn> </apply> </apply> <apply> <times /> <ci>I_NCX</ci> <cn>3</cn> </apply> </apply> <ci>INa_NSC</ci> </apply> </math> INa_totm = INa_NaKCl+INa_SOC+I_NaK*3+I_NCX*3+INa_NSC IP3_0 Intracellular inositol trisphosphate concentration false Rate of change of intracellular inositol trisphosphate concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <minus /> <apply> <divide /> <apply> <times /> <ci>r_hG</ci> <ci>PIP2</ci> </apply> <ci>gamma_G</ci> </apply> <apply> <times /> <apply> <times /> <ci>k_degG</ci> <ci>IP3</ci> </apply> <cn>1E-15</cn> </apply> </apply> <cn>1E15</cn> </apply> </math> IP3:time = (r_hG*PIP2/gamma_G-k_degG*IP3*1E-15)*1E15 Initial intracellular inositol trisphosphate concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>0</cn> </math> IP3_0 = 0 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <minus /> <apply> <divide /> <apply> <times /> <ci>r_hG</ci> <ci>PIP2</ci> </apply> <ci>gamma_G</ci> </apply> <apply> <times /> <apply> <times /> <ci>k_degG</ci> <ci>IP3</ci> </apply> <cn>1E-15</cn> </apply> </apply> <cn>1E15</cn> </apply> </math> IP3:time = (r_hG*PIP2/gamma_G-k_degG*IP3*1E-15)*1E15 Chemical concentration http://bhi.washington.edu/OPB#OPB_00340 IP3 receptor calcium current Caclium current through the inositol trisphosphate receptor on the sarcoplasmic reticulum 1.0 1.0 Total cell large conductance calcium activated potassium channel current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <times /> <apply> <times /> <ci>A_m</ci> <ci>N_BKCa</ci> </apply> <ci>P_KCa</ci> </apply> <ci>i_KCa</ci> </apply> </math> I_BKCa = A_m*N_BKCa*P_KCa*i_KCa Charge flow rate http://bhi.washington.edu/OPB#OPB_00318 Total cell calcium activated chloride channel current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <times /> <apply> <times /> <ci>C_m</ci> <ci>g_ClCa</ci> </apply> <ci>P_Cl</ci> </apply> <apply> <minus /> <ci>V_m</ci> <ci>E_Cl</ci> </apply> </apply> </math> I_ClCa = C_m*g_ClCa*P_Cl*(V_m-E_Cl) Charge flow rate http://bhi.washington.edu/OPB#OPB_00318 Total cell IP3 receptor calcium current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <ci>Ibar_IP3</ci> <ci>z_Ca</ci> </apply> <ci>Vol_Ca</ci> </apply> <ci>F</ci> </apply> <apply> <power /> <apply> <times /> <apply> <times /> <apply> <divide /> <ci>IP3</ci> <apply> <plus /> <ci>IP3</ci> <ci>K_IP3</ci> </apply> </apply> <apply> <divide /> <ci>Ca_i</ci> <apply> <plus /> <ci>Ca_i</ci> <ci>K_actIP3</ci> </apply> </apply> </apply> <ci>h_IP3</ci> </apply> <cn>3</cn> </apply> </apply> <apply> <minus /> <ci>Ca_u</ci> <ci>Ca_i</ci> </apply> </apply> </math> I_IP3 = Ibar_IP3*z_Ca*Vol_Ca*F*(IP3/(IP3+K_IP3)*(Ca_i/(Ca_i+K_actIP3))*h_IP3)^3*(Ca_u-Ca_i) Charge flow rate http://bhi.washington.edu/OPB#OPB_00318 Total cell potassium leak channel current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <ci>g_Kleak</ci> <apply> <minus /> <ci>V_m</ci> <ci>E_K</ci> </apply> </apply> </math> I_Kleak = g_Kleak*(V_m-E_K) Charge flow rate http://bhi.washington.edu/OPB#OPB_00318 Total cell voltage gated potassium channel current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <times /> <apply> <times /> <ci>g_Kv</ci> <ci>p_K</ci> </apply> <apply> <plus /> <apply> <times /> <ci>q_1</ci> <cn>.45</cn> </apply> <apply> <times /> <ci>q_2</ci> <cn>.55</cn> </apply> </apply> </apply> <apply> <minus /> <ci>V_m</ci> <ci>E_K</ci> </apply> </apply> </math> I_Kv = g_Kv*p_K*(q_1*.45+q_2*.55)*(V_m-E_K) Charge flow rate http://bhi.washington.edu/OPB#OPB_00318 Total cell sodium/calcium exchanger current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <times /> <apply> <times /> <ci>g_NCX</ci> <ci>R_NCXcGMP</ci> </apply> <apply> <minus /> <apply> <times /> <apply> <times /> <apply> <power /> <ci>Na_i</ci> <cn>3</cn> </apply> <ci>Ca_e</ci> </apply> <ci>phi_F</ci> </apply> <apply> <times /> <apply> <times /> <apply> <power /> <ci>Na_e</ci> <cn>3</cn> </apply> <ci>Ca_i</ci> </apply> <ci>phi_R</ci> </apply> </apply> </apply> <apply> <plus /> <cn>1</cn> <apply> <times /> <ci>d_NCX</ci> <apply> <plus /> <apply> <times /> <apply> <power /> <ci>Na_e</ci> <cn>3</cn> </apply> <ci>Ca_i</ci> </apply> <apply> <times /> <apply> <power /> <ci>Na_i</ci> <cn>3</cn> </apply> <ci>Ca_e</ci> </apply> </apply> </apply> </apply> </apply> </math> I_NCX = g_NCX*R_NCXcGMP*(Na_i^3*Ca_e*phi_F-Na_e^3*Ca_i*phi_R)/(1+d_NCX*(Na_e^3*Ca_i+Na_i^3*Ca_e)) Charge flow rate http://bhi.washington.edu/OPB#OPB_00318 Total cell nonselective cation channel current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <plus /> <apply> <plus /> <ci>INa_NSC</ci> <ci>IK_NSC</ci> </apply> <ci>ICa_NSC</ci> </apply> </math> I_NSC = INa_NSC+IK_NSC+ICa_NSC Charge flow rate http://bhi.washington.edu/OPB#OPB_00318 Total cell sodium/potassium ATPase current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <times /> <apply> <divide /> <apply> <times /> <apply> <divide /> <apply> <times /> <apply> <times /> <apply> <times /> <ci>C_m</ci> <ci>Ibar_NaK</ci> </apply> <ci>Q</ci> </apply> <apply> <power /> <apply> <divide /> <ci>K_e</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">1</cn> </apply> <ci>n_HKe</ci> </apply> </apply> <apply> <plus /> <apply> <power /> <apply> <divide /> <ci>K_e</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">1</cn> </apply> <ci>n_HKe</ci> </apply> <apply> <power /> <apply> <divide /> <ci>K_dKe</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">1</cn> </apply> <ci>n_HKe</ci> </apply> </apply> </apply> <apply> <power /> <apply> <divide /> <ci>Na_i</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">1</cn> </apply> <ci>n_HNai</ci> </apply> </apply> <apply> <plus /> <apply> <power /> <apply> <divide /> <ci>Na_i</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">1</cn> </apply> <ci>n_HNai</ci> </apply> <apply> <power /> <apply> <divide /> <ci>Na_dNai</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">1</cn> </apply> <ci>n_HNai</ci> </apply> </apply> </apply> <apply> <plus /> <ci>V_m</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">150</cn> </apply> </apply> <apply> <plus /> <ci>V_m</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">200</cn> </apply> </apply> </math> I_NaK = C_m*Ibar_NaK*Q*(K_e/1)^n_HKe/((K_e/1)^n_HKe+(K_dKe/1)^n_HKe)*(Na_i/1)^n_HNai/((Na_i/1)^n_HNai+(Na_dNai/1)^n_HNai)*(V_m+150)/(V_m+200) Charge flow rate http://bhi.washington.edu/OPB#OPB_00318 Total cell plasma membrane calcium ATPase current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <ci>Ibar_PMCA</ci> <apply> <divide /> <ci>Ca_i</ci> <apply> <plus /> <ci>Ca_i</ci> <ci>K_mPMCA</ci> </apply> </apply> </apply> </math> I_PMCA = Ibar_PMCA*(Ca_i/(Ca_i+K_mPMCA)) Charge flow rate http://bhi.washington.edu/OPB#OPB_00318 Total cell sarcoplasmic/endoplamic reticulum calcium APTase current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <ci>Ibar_SERCA</ci> <apply> <divide /> <ci>Ca_i</ci> <apply> <plus /> <ci>Ca_i</ci> <ci>K_mup</ci> </apply> </apply> </apply> </math> I_SERCA = Ibar_SERCA*(Ca_i/(Ca_i+K_mup)) Charge flow rate http://bhi.washington.edu/OPB#OPB_00318 Total cell store operated cation channel current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <plus /> <ci>INa_SOC</ci> <ci>ICa_SOC</ci> </apply> </math> I_SOC = INa_SOC+ICa_SOC Charge flow rate http://bhi.washington.edu/OPB#OPB_00318 Total cell L-type calcium channel current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <ci>A_m</ci> <ci>P_VOCC</ci> </apply> <ci>d_L</ci> </apply> <ci>f_L</ci> </apply> <ci>V_m</ci> </apply> <apply> <times /> <apply> <times /> <apply> <power /> <ci>z_Ca</ci> <cn>2</cn> </apply> <ci>F</ci> </apply> <ci>FRT</ci> </apply> </apply> <apply> <minus /> <ci>Ca_e</ci> <apply> <times /> <ci>Ca_i</ci> <apply> <exp /> <apply> <times /> <apply> <times /> <ci>V_m</ci> <ci>z_Ca</ci> </apply> <ci>FRT</ci> </apply> </apply> </apply> </apply> </apply> <apply> <minus /> <cn>1</cn> <apply> <exp /> <apply> <times /> <apply> <times /> <ci>V_m</ci> <ci>z_Ca</ci> </apply> <ci>FRT</ci> </apply> </apply> </apply> </apply> <cn>1E6</cn> </apply> </math> I_VOCC = A_m*P_VOCC*d_L*f_L*V_m*(z_Ca^2*F*FRT)*(Ca_e-Ca_i*exp(V_m*z_Ca*FRT))/(1-exp(V_m*z_Ca*FRT))*1000000.0000000003 Charge flow rate http://bhi.washington.edu/OPB#OPB_00318 Total cell ryanodine receptor calcium current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <plus /> <apply> <power /> <ci>R_10</ci> <cn>2</cn> </apply> <ci>R_leak</ci> </apply> <apply> <minus /> <ci>Ca_r</ci> <ci>Ca_i</ci> </apply> </apply> <ci>z_Ca</ci> </apply> <ci>F</ci> </apply> <ci>Vol_SRr</ci> </apply> <ci>tau_rel</ci> </apply> </math> I_rel = (R_10^2+R_leak)*(Ca_r-Ca_i)*z_Ca*F*Vol_SRr/tau_rel Charge flow rate http://bhi.washington.edu/OPB#OPB_00318 Input applied stimulation current Total cell transfer from SR matrix to SR cisternae calcium current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <minus /> <ci>Ca_u</ci> <ci>Ca_r</ci> </apply> <ci>z_Ca</ci> </apply> <ci>F</ci> </apply> <ci>Vol_SRu</ci> </apply> <ci>tau_tr</ci> </apply> </math> I_tr = (Ca_u-Ca_r)*z_Ca*F*Vol_SRu/tau_tr Charge flow rate http://bhi.washington.edu/OPB#OPB_00318 Total cell IP3 receptor maximal rate of calcium release <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.00288</cn> </math> Ibar_IP3 = .00288 Total cell sodium/potassium ATPase maximal current <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>2.3083</cn> </math> Ibar_NaK = 2.3083 Total cell plasma membrane calcium ATPase maximal calcium current <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>5.37</cn> </math> Ibar_PMCA = 5.37 Total cell sarcoplasmic/endoplasmic reticulum calcium ATPase maximal current <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>6.68</cn> </math> Ibar_SERCA = 6.68 Internal SR calcium current Total cell transfer from SR matrix to SR cisternae calcium current 1.0 1.0 Alpha adrenoceptor unphosporylated dissociation constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.01</cn> </math> K_1G = .01 Alpha adrenoceptor phosporylated dissociation constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.2</cn> </math> K_2G = .2 Binding affinity of calsequestrin in sarcoplasmic reticulum <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.8</cn> </math> K_CSQN = .8 Calcium activated chloride channel calcium activation effective concentration at 50% maximal response <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>3.65E-4</cn> </math> K_ClCa = 3.65E-4 Calcium activated chloride channel cyclic GMP sensitivity parameter <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <minus /> <cn>1</cn> <apply> <times /> <ci>alpha_Cl</ci> <cn>.9</cn> </apply> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">4E-4</cn> </apply> </math> K_ClCacGMP = (1-alpha_Cl*.9)*4E-4 Calcium activated chloride channel cyclic GMP activation effective concentration at 50% maximal response <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>6.4</cn> </math> K_ClcGMP = 6.4 IP3 receptor IP3 dissociation constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1.2E-4</cn> </math> K_IP3 = 1.2E-4 Nonselective cation channel DAG concentration at 50% maximal response <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.003</cn> </math> K_NSC = .003 Store operated cation channel calcium concentration at 50% maiximal response <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1E-4</cn> </math> K_SOC = 1E-4 IP3 receptor calcium activation dissociation constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1.7E-4</cn> </math> K_actIP3 = 1.7E-4 Calcium - phospolipase C dissociation constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>4E-4</cn> </math> K_cG = 4E-4 Nonspecific calcium buffer dissociation constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>5.298E-4</cn> </math> K_dB = 5.298E-4 Calmoduling-calcium dissociation constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>2.6E-4</cn> </math> K_dCM = 2.6E-4 Sodium/potassium ATPase extracellular potassium binding rate <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1.6</cn> </math> K_dKe = 1.6 Extracellular potassium concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>5</cn> </math> K_e = 5 Chemical concentration http://bhi.washington.edu/OPB#OPB_00340 K_i0 Intracellular potassium concentration false Rate of change of intracellular potassium concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <ci>IK_totm</ci> <apply> <times /> <ci>F</ci> <ci>Vol_i</ci> </apply> </apply> <cn>-1</cn> </apply> </math> K_i:time = IK_totm/(F*Vol_i)*(-1) Initial intracellular potassium concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>140</cn> </math> K_i0 = 140 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <ci>IK_totm</ci> <apply> <times /> <ci>F</ci> <ci>Vol_i</ci> </apply> </apply> <cn>-1</cn> </apply> </math> K_i:time = IK_totm/(F*Vol_i)*(-1) Chemical concentration http://bhi.washington.edu/OPB#OPB_00340 IP3 receptor calcium inhibition dissociation constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1E-4</cn> </math> K_inhIP3 = 1E-4 Plasma membrane calcium ATPase Michaelis constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1.7E-4</cn> </math> K_mPMCA = 1.7E-4 Soluble guanylate cyclase activation and cyclic GMP formation parameter <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.001</cn> </math> K_mpde = .001 Sarcoplasmic reticulum ryanodine receptor rate of calcium unbinding from activation site <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.0076</cn> </math> K_mr1 = .0076 Sarcoplasmic reticulum ryanodine receptor rate of calcium unbinding from inactivation site <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.084</cn> </math> K_mr2 = .084 Sarcoplasmic/endoplasmic reticulum calcium ATPase Michaelis constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.001</cn> </math> K_mup = .001 Sarcoplasmic reticulum ryanodine receptor rate of calcium binding to activation site <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>2500</cn> </math> K_r1 = 2500 Sarcoplasmic reticulum ryanodine receptor rate of calcium binding to inactivation site <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1.05</cn> </math> K_r2 = 1.05 L-type calcium channel current Total cell L-type calcium channel current 1.0 1.0 Sodium/potassium/chloride contransporter scaled permeability parameter <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1.79E-17</cn> </math> L_NaKCl = 1.79E-17 Large conductance calcium activated potassium channel current Total large conductance calcium activated potassium channel current 1.0 1.0 Extracellular norepinephrine concentration Chemical concentration http://bhi.washington.edu/OPB#OPB_00340 Intracellular nitric oxide concentration Initial intracellular nitric oxide concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1E-12</cn> </math> NO_0 = 1E-12 Chemical concentration http://bhi.washington.edu/OPB#OPB_00340 Avogadro constant http://bhi.washington.edu/OPB#OPB_01622 Avogadros number <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>6.022E23</cn> </math> N_Avo = 6.022E23 Large conductance calcium activated potassium channel density per unit cell surface area <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>6.6E6</cn> </math> N_BKCa = 6.6E6 Sodium/potassium ATPase intracellular sodium binding rate <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>22</cn> </math> Na_dNai = 22 Extracellular sodium concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>140</cn> </math> Na_e = 140 Chemical concentration http://bhi.washington.edu/OPB#OPB_00340 Na_i0 Intracellular sodium concentration false Rate of change of intracellular sodium concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <ci>INa_totm</ci> <apply> <times /> <ci>F</ci> <ci>Vol_i</ci> </apply> </apply> <cn>-1</cn> </apply> </math> Na_i:time = INa_totm/(F*Vol_i)*(-1) Initial intracellular sodium concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>8.4</cn> </math> Na_i0 = 8.4 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <ci>INa_totm</ci> <apply> <times /> <ci>F</ci> <ci>Vol_i</ci> </apply> </apply> <cn>-1</cn> </apply> </math> Na_i:time = INa_totm/(F*Vol_i)*(-1) Chemical concentration http://bhi.washington.edu/OPB#OPB_00340 Nonselective cation channel calcium current Total cell nonselective cation channel calcium current 1.0 1.0 Nonselective cation channel whole cell calcium permeability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <ci>PNa_NSC</ci> <cn>4.54</cn> </apply> </math> PCa_NSC = PNa_NSC*4.54 PIP2_0 Number of cytosolic phosphatidylinositol 4,5-bisphosphate molecules false Rate of change of number of cytosolic phosphatidylinositol 4,5-bisphosphate molecules <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <plus /> <apply> <minus /> <apply> <times /> <apply> <times /> <apply> <plus /> <ci>r_hG</ci> <ci>r_rG</ci> </apply> <ci>PIP2</ci> </apply> <cn>-1</cn> </apply> <apply> <times /> <apply> <times /> <apply> <times /> <ci>r_rG</ci> <ci>gamma_G</ci> </apply> <ci>IP3</ci> </apply> <cn>1E-15</cn> </apply> </apply> <apply> <times /> <ci>r_rG</ci> <ci>PIP2_T</ci> </apply> </apply> </math> PIP2:time = (r_hG+r_rG)*PIP2*(-1)-r_rG*gamma_G*IP3*1E-15+r_rG*PIP2_T Initial number of cytosolic phosphatidylinositol 4,5-bisphosphate molecules <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <minus /> <ci>PIP2_T</ci> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <plus /> <cn>1</cn> <apply> <divide /> <ci>k_degG</ci> <ci>r_rG</ci> </apply> </apply> <ci>gamma_G</ci> </apply> <ci>IP3_0</ci> </apply> <cn>1E-15</cn> </apply> </apply> </math> PIP2_0 = PIP2_T-(1+k_degG/r_rG)*gamma_G*IP3_0*1E-15 Total number of phosphatidylinositol 4,5-bisphosphate molecules <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>5E7</cn> </math> PIP2_T = 5E7 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <plus /> <apply> <minus /> <apply> <times /> <apply> <times /> <apply> <plus /> <ci>r_hG</ci> <ci>r_rG</ci> </apply> <ci>PIP2</ci> </apply> <cn>-1</cn> </apply> <apply> <times /> <apply> <times /> <apply> <times /> <ci>r_rG</ci> <ci>gamma_G</ci> </apply> <ci>IP3</ci> </apply> <cn>1E-15</cn> </apply> </apply> <apply> <times /> <ci>r_rG</ci> <ci>PIP2_T</ci> </apply> </apply> </math> PIP2:time = (r_hG+r_rG)*PIP2*(-1)-r_rG*gamma_G*IP3*1E-15+r_rG*PIP2_T Particle count http://bhi.washington.edu/OPB#OPB_01001 Nonselective cation channel whole cell potasium permeability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <ci>PNa_NSC</ci> <cn>1.06</cn> </apply> </math> PK_NSC = PNa_NSC*1.06 Nonselective cation channel whole cell sodium permeability <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>5.11E-7</cn> </math> PNa_NSC = 5.11E-7 calsequestrin-2 http://purl.obolibrary.org/obo/PR_000005057 calmodulin (human) http://purl.obolibrary.org/obo/PR_P62158 Large conductance calcium activated potassium channel permeability surface area product <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>3.9E-13</cn> </math> P_BKCa = 3.9E-13 Calcium activated chloride channel activation gate open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <plus /> <apply> <times /> <ci>R_ClcGMPmin</ci> <apply> <divide /> <apply> <power /> <apply> <divide /> <ci>Ca_i</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">1</cn> </apply> <ci>n_ClCa</ci> </apply> <apply> <plus /> <apply> <power /> <apply> <divide /> <ci>Ca_i</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">1</cn> </apply> <ci>n_ClCa</ci> </apply> <apply> <power /> <apply> <divide /> <ci>K_ClCa</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">1</cn> </apply> <ci>n_ClCa</ci> </apply> </apply> </apply> </apply> <apply> <times /> <ci>alpha_Cl</ci> <apply> <divide /> <apply> <power /> <apply> <divide /> <ci>Ca_i</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">1</cn> </apply> <ci>n_ClCa</ci> </apply> <apply> <plus /> <apply> <power /> <apply> <divide /> <ci>Ca_i</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">1</cn> </apply> <ci>n_ClCa</ci> </apply> <apply> <power /> <apply> <divide /> <ci>K_ClCacGMP</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">1</cn> </apply> <ci>n_ClCa</ci> </apply> </apply> </apply> </apply> </apply> </math> P_Cl = R_ClcGMPmin*((Ca_i/1)^n_ClCa/((Ca_i/1)^n_ClCa+(K_ClCa/1)^n_ClCa))+alpha_Cl*((Ca_i/1)^n_ClCa/((Ca_i/1)^n_ClCa+(K_ClCacGMP/1)^n_ClCa)) Large conductance calcium activated potassium channel total open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <plus /> <apply> <times /> <ci>p_f</ci> <cn>.17</cn> </apply> <apply> <times /> <ci>p_s</ci> <cn>.83</cn> </apply> </apply> </math> P_KCa = p_f*.17+p_s*.83 0 Store operated cation channel activation gate open probability false Rate of change of store operated cation channel activation gate open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <ci>Pbar_SOC</ci> <ci>P_SOC</ci> </apply> <ci>tau_SOC</ci> </apply> </math> P_SOC:time = (Pbar_SOC-P_SOC)/tau_SOC Initial store operated cation channel activation gate open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>0</cn> </math> P_SOC0 = 0 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <ci>Pbar_SOC</ci> <ci>P_SOC</ci> </apply> <ci>tau_SOC</ci> </apply> </math> P_SOC:time = (Pbar_SOC-P_SOC)/tau_SOC L-type calcium channel maximal calcium permeability <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1.88E-5</cn> </math> P_VOCC = 1.88E-5 Store operated cation channel activation gate steady state open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <cn>1</cn> <apply> <plus /> <cn>1</cn> <apply> <divide /> <ci>Ca_u</ci> <ci>K_SOC</ci> </apply> </apply> </apply> </math> Pbar_SOC = 1/(1+Ca_u/K_SOC) Plasma membrane calcium ATPase current Total cell plasma membrane calcium ATPase current 1.0 1.0 Nonselective cation channel activation gate steady state open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <plus /> <cn>.4344</cn> <apply> <divide /> <cn>.5656</cn> <apply> <plus /> <cn>1</cn> <apply> <exp /> <apply> <times /> <apply> <divide /> <apply> <minus /> <ci>V_m</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">47.12</cn> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">24.24</cn> </apply> <cn>-1</cn> </apply> </apply> </apply> </apply> </apply> </math> Po_NSC = .4344+.5656/(1+exp((V_m-47.12)/24.24*(-1))) Portion of the cytosol available to calcium Potassium leak channel Sodium/calcium exchanger temperature correction factor Sodium/calcium exchanger temperature correction multiplier <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1.87</cn> </math> Q_10 = 1.87 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <power /> <ci>Q_10</ci> <apply> <divide /> <apply> <minus /> <ci>T</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="K">309.15</cn> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="K">10</cn> </apply> </apply> </math> Q = Q_10^((T-309.15)/10) Ideal gas constant http://bhi.washington.edu/OPB#OPB_01705 Ideal gas constant Product of ideal gas number and temperature <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <ci>R</ci> <ci>T</ci> </apply> </math> RT = R*T Ryanodine receptor state with no active site or inactive site calcium bond <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <minus /> <apply> <minus /> <apply> <minus /> <cn>1</cn> <ci>R_10</ci> </apply> <ci>R_11</ci> </apply> <ci>R_01</ci> </apply> </math> R_00 = 1-R_10-R_11-R_01 State fraction of chemical http://bhi.washington.edu/OPB#OPB_01298 R_010 Ryanodine receptor state with calcium bound to the inactivation site false Rate of change of ryanodine receptor state with calcium bound to the inactivation site <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <minus /> <apply> <plus /> <apply> <times /> <apply> <times /> <ci>K_r2</ci> <ci>Ca_i</ci> </apply> <ci>R_00</ci> </apply> <apply> <times /> <ci>K_mr1</ci> <ci>R_11</ci> </apply> </apply> <apply> <times /> <apply> <plus /> <ci>K_mr2</ci> <apply> <times /> <ci>K_r1</ci> <apply> <power /> <ci>Ca_i</ci> <cn>2</cn> </apply> </apply> </apply> <ci>R_01</ci> </apply> </apply> </math> R_01:time = K_r2*Ca_i*R_00+K_mr1*R_11-(K_mr2+K_r1*Ca_i^2)*R_01 Initial ryanodine receptor state with calcium bound to the inactivation site <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.9955</cn> </math> R_010 = .9955 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <minus /> <apply> <plus /> <apply> <times /> <apply> <times /> <ci>K_r2</ci> <ci>Ca_i</ci> </apply> <ci>R_00</ci> </apply> <apply> <times /> <ci>K_mr1</ci> <ci>R_11</ci> </apply> </apply> <apply> <times /> <apply> <plus /> <ci>K_mr2</ci> <apply> <times /> <ci>K_r1</ci> <apply> <power /> <ci>Ca_i</ci> <cn>2</cn> </apply> </apply> </apply> <ci>R_01</ci> </apply> </apply> </math> R_01:time = K_r2*Ca_i*R_00+K_mr1*R_11-(K_mr2+K_r1*Ca_i^2)*R_01 State fraction of chemical http://bhi.washington.edu/OPB#OPB_01298 R_100 Ryanodine receptor state with calcium bound to the activation site false Rate of change of ryanodine receptor state with calcium bound to the activation site <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <plus /> <apply> <minus /> <apply> <times /> <apply> <times /> <ci>K_r1</ci> <apply> <power /> <ci>Ca_i</ci> <cn>2</cn> </apply> </apply> <ci>R_00</ci> </apply> <apply> <times /> <apply> <plus /> <ci>K_mr1</ci> <apply> <times /> <ci>K_r2</ci> <ci>Ca_i</ci> </apply> </apply> <ci>R_10</ci> </apply> </apply> <apply> <times /> <ci>K_mr2</ci> <ci>R_11</ci> </apply> </apply> </math> R_10:time = K_r1*Ca_i^2*R_00-(K_mr1+K_r2*Ca_i)*R_10+K_mr2*R_11 Initial ryanodine receptor state with calcium bound to the activation site <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.0033</cn> </math> R_100 = .0033 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <plus /> <apply> <minus /> <apply> <times /> <apply> <times /> <ci>K_r1</ci> <apply> <power /> <ci>Ca_i</ci> <cn>2</cn> </apply> </apply> <ci>R_00</ci> </apply> <apply> <times /> <apply> <plus /> <ci>K_mr1</ci> <apply> <times /> <ci>K_r2</ci> <ci>Ca_i</ci> </apply> </apply> <ci>R_10</ci> </apply> </apply> <apply> <times /> <ci>K_mr2</ci> <ci>R_11</ci> </apply> </apply> </math> R_10:time = K_r1*Ca_i^2*R_00-(K_mr1+K_r2*Ca_i)*R_10+K_mr2*R_11 State fraction of chemical http://bhi.washington.edu/OPB#OPB_01298 R_110 Ryanodine receptor state with calcium bound to both the activation and inactivation sites false Rate of change of ryanodine receptor state with calcium bound to both the activation and inactivation sites <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <plus /> <apply> <minus /> <apply> <times /> <apply> <times /> <ci>K_r2</ci> <ci>Ca_i</ci> </apply> <ci>R_10</ci> </apply> <apply> <times /> <apply> <plus /> <ci>K_mr1</ci> <ci>K_mr2</ci> </apply> <ci>R_11</ci> </apply> </apply> <apply> <times /> <apply> <times /> <ci>K_r1</ci> <apply> <power /> <ci>Ca_i</ci> <cn>2</cn> </apply> </apply> <ci>R_01</ci> </apply> </apply> </math> R_11:time = K_r2*Ca_i*R_10-(K_mr1+K_mr2)*R_11+K_r1*Ca_i^2*R_01 Initial ryanodine receptor state with calcium bound to both the activation and inactivation sites <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>4E-6</cn> </math> R_110 = 4E-6 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <plus /> <apply> <minus /> <apply> <times /> <apply> <times /> <ci>K_r2</ci> <ci>Ca_i</ci> </apply> <ci>R_10</ci> </apply> <apply> <times /> <apply> <plus /> <ci>K_mr1</ci> <ci>K_mr2</ci> </apply> <ci>R_11</ci> </apply> </apply> <apply> <times /> <apply> <times /> <ci>K_r1</ci> <apply> <power /> <ci>Ca_i</ci> <cn>2</cn> </apply> </apply> <ci>R_01</ci> </apply> </apply> </math> R_11:time = K_r2*Ca_i*R_10-(K_mr1+K_mr2)*R_11+K_r1*Ca_i^2*R_01 State fraction of chemical http://bhi.washington.edu/OPB#OPB_01298 Calcium activated chloride channel cyclic GMP independent factor <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.0132</cn> </math> R_ClcGMPmin = .0132 Sodium/calcium exchanger cyclic GMP sensitivity <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <plus /> <cn>1</cn> <apply> <times /> <apply> <divide /> <ci>cGMP_i</ci> <apply> <plus /> <ci>cGMP_i</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">.045</cn> </apply> </apply> <cn>.55</cn> </apply> </apply> </math> R_NCXcGMP = 1+cGMP_i/(cGMP_i+.045)*.55 Large conductance calcium activated potassium channel nitric oxide sensitivity Initial large conductance calcium activated potassium channel nitric oxide sensitivity <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <ci>NO_0</ci> <apply> <plus /> <ci>NO_0</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">2E-4</cn> </apply> </apply> </math> R_NO0 = NO_0/(NO_0+2E-4) <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <ci>NO</ci> <apply> <plus /> <ci>NO</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">2E-4</cn> </apply> </apply> </math> R_NO = NO/(NO+2E-4) Sodium/potassium/chloride cotransporter cyclic GMP sensitivity <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <plus /> <cn>1</cn> <apply> <times /> <apply> <divide /> <ci>cGMP_i</ci> <apply> <plus /> <ci>cGMP_i</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">.0064</cn> </apply> </apply> <cn>3.5</cn> </apply> </apply> </math> R_NaKClcGMP = 1+cGMP_i/(cGMP_i+.0064)*3.5 Total number of alpha adrenoreceptors <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>2E4</cn> </math> R_TG = 2E4 Large conductance calcium activated potassium channel cyclic GMP sensitivity factor Large conductance calcium activated potassium channel cyclic GMP regulatory factor <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <power /> <ci>cGMP_i0</ci> <cn>2</cn> </apply> <apply> <plus /> <apply> <power /> <ci>cGMP_i0</ci> <cn>2</cn> </apply> <apply> <times /> <apply> <power /> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="uM">5.5E-4</cn> <cn>2</cn> </apply> <cn>1E-6</cn> </apply> </apply> </apply> </math> R_cGMP0 = cGMP_i0^2/(cGMP_i0^2+5.5E-4^2*9.999999999999995E-7) <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <power /> <ci>cGMP_i</ci> <cn>2</cn> </apply> <apply> <plus /> <apply> <power /> <ci>cGMP_i</ci> <cn>2</cn> </apply> <apply> <power /> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">.0015</cn> <cn>2</cn> </apply> </apply> </apply> </math> R_cGMP = cGMP_i^2/(cGMP_i^2+.0015^2) <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>8314.472</cn> </math> R = 8314.472 Ryanodine receptor calcium leak factor <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1.07E-5</cn> </math> R_leak = 1.07E-5 R_supSG0 Number of unphosporylated alpha adrenoreceptors false Rate of change of number of unphosporylated alpha adrenoreceptors <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <minus /> <apply> <minus /> <apply> <times /> <apply> <times /> <ci>k_rG</ci> <ci>xi_G</ci> </apply> <ci>R_TG</ci> </apply> <apply> <times /> <apply> <plus /> <ci>k_rG</ci> <apply> <divide /> <apply> <times /> <ci>k_pG</ci> <ci>NE</ci> </apply> <apply> <plus /> <ci>K_1G</ci> <ci>NE</ci> </apply> </apply> </apply> <ci>R_supSG</ci> </apply> </apply> <apply> <times /> <ci>k_rG</ci> <ci>R_supSPG</ci> </apply> </apply> </math> R_supSG:time = k_rG*xi_G*R_TG-(k_rG+k_pG*NE/(K_1G+NE))*R_supSG-k_rG*R_supSPG Initial number of unphosporylated alpha adrenoreceptors <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <ci>R_TG</ci> <ci>xi_G</ci> </apply> </math> R_supSG0 = R_TG*xi_G <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <minus /> <apply> <minus /> <apply> <times /> <apply> <times /> <ci>k_rG</ci> <ci>xi_G</ci> </apply> <ci>R_TG</ci> </apply> <apply> <times /> <apply> <plus /> <ci>k_rG</ci> <apply> <divide /> <apply> <times /> <ci>k_pG</ci> <ci>NE</ci> </apply> <apply> <plus /> <ci>K_1G</ci> <ci>NE</ci> </apply> </apply> </apply> <ci>R_supSG</ci> </apply> </apply> <apply> <times /> <ci>k_rG</ci> <ci>R_supSPG</ci> </apply> </apply> </math> R_supSG:time = k_rG*xi_G*R_TG-(k_rG+k_pG*NE/(K_1G+NE))*R_supSG-k_rG*R_supSPG R_supSPG0 Number of phosporylated alpha adrenoreceptors false Rate of change of number of phosporylated alpha adrenoreceptors <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <ci>NE</ci> <apply> <minus /> <apply> <divide /> <apply> <times /> <ci>k_pG</ci> <ci>R_supSG</ci> </apply> <apply> <plus /> <ci>K_1G</ci> <ci>NE</ci> </apply> </apply> <apply> <divide /> <apply> <times /> <ci>k_eG</ci> <ci>R_supSPG</ci> </apply> <apply> <plus /> <ci>K_2G</ci> <ci>NE</ci> </apply> </apply> </apply> </apply> </math> R_supSPG:time = NE*(k_pG*R_supSG/(K_1G+NE)-k_eG*R_supSPG/(K_2G+NE)) Initial number of phosporylated alpha adrenoreceptors <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>0</cn> </math> R_supSPG0 = 0 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <ci>NE</ci> <apply> <minus /> <apply> <divide /> <apply> <times /> <ci>k_pG</ci> <ci>R_supSG</ci> </apply> <apply> <plus /> <ci>K_1G</ci> <ci>NE</ci> </apply> </apply> <apply> <divide /> <apply> <times /> <ci>k_eG</ci> <ci>R_supSPG</ci> </apply> <apply> <plus /> <ci>K_2G</ci> <ci>NE</ci> </apply> </apply> </apply> </apply> </math> R_supSPG:time = NE*(k_pG*R_supSG/(K_1G+NE)-k_eG*R_supSPG/(K_2G+NE)) Ryanodine receptor 2 with calcium bound to both the activation and inactivation sites Ryanodine receptor 2 with calcium bound to inactivation site Ryanodine receptor 2 with calcium bound to the activation site Ryanodine receptor 2 with no calcium bound Ryanodine receptor calcium current Total cell ryanodine receptor calcium current 1.0 1.0 Sarcoplasmic/endoplamic reticulum calcium APTase current Total cell sarcoplasmic/endoplamic reticulum calcium APTase current 1.0 1.0 Average cytosolic calmodulin concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.1</cn> </math> Sbar_CM = .1 Chemical concentration http://bhi.washington.edu/OPB#OPB_00340 Sodium/calcium exchanger current Total cell sodium/calcium exchanger current 3.0 1.0 1.0 3.0 Sodium/potassium ATPase current Total cell sodium/potassium ATPase current 2.0 3.0 3.0 2.0 Store operated cation channel Store operated cation channel current Total cell store operated cation channel current 1.0 1.0 1.0 1.0 Temperature <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>293</cn> </math> T = 293 Temperature http://bhi.washington.edu/OPB#OPB_00293 Total nonselective cation channel current Total cell nonselective cation channel current comprised of the calcium, potassium and sodium currents 1.0 1.0 1.0 1.0 1.0 1.0 1/(ms*mM) 1/(ms*mM^2) 1/cm^2 1/mV 1/mol 1/mol*picoliter 1/ms 1/ms*1/mol*picoliter*mM 1/msec K amp true candela true cm/s cm^2 cm^3/s coulomb*mV/(K*mol) coulomb*mV/mol coulomb/mol degK true dimensionless kg true m true mM mM/ms mM/ms/msec mM/msec mM^2 mV mV/msec mol true mol^2/(J*s*cm^2) ms msec nanosiemens nanosiemens/picofarad picoampere picoampere/picofarad picofarad picofarad/cm^2 picoliter sec true uM Large conductance calcium activated potassium channel voltage at 50% maximal response Initial large conductance calcium activated potassium channel voltage at 50% maximal response <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <minus /> <apply> <minus /> <apply> <minus /> <apply> <times /> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">-41.7</cn> <apply> <log /> <apply> <divide /> <ci>Ca_i0</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">1</cn> </apply> </apply> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">128.2</cn> </apply> <apply> <times /> <ci>dV_50KCaNO</ci> <ci>R_NO0</ci> </apply> </apply> <apply> <times /> <ci>dV_50KCacGMP</ci> <ci>R_cGMP0</ci> </apply> </apply> </math> V_50KCa0 = (-41.7)*log(Ca_i0/1)-128.2-dV_50KCaNO*R_NO0-dV_50KCacGMP*R_cGMP0 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <minus /> <apply> <minus /> <apply> <minus /> <apply> <times /> <apply> <times /> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">41.7</cn> <apply> <log /> <apply> <divide /> <ci>Ca_i</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">1</cn> </apply> </apply> </apply> <cn>-1</cn> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">128.2</cn> </apply> <apply> <times /> <ci>dV_50KCaNO</ci> <ci>R_NO</ci> </apply> </apply> <apply> <times /> <ci>dV_50KCacGMP</ci> <ci>R_cGMP</ci> </apply> </apply> </math> V_50KCa = 41.7*log(Ca_i/1)*(-1)-128.2-dV_50KCaNO*R_NO-dV_50KCacGMP*R_cGMP V_cGMP0 Reaction velocity of cyclic GMP formation false Rate of change of reaction velocity of cyclic GMP formation <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <ci>Vbar_cGMP</ci> <ci>V_cGMP</ci> </apply> <ci>tau_sGC</ci> </apply> </math> V_cGMP:time = (Vbar_cGMP-V_cGMP)/tau_sGC Initial reaction velocity of cyclic GMP formation <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>0</cn> </math> V_cGMP0 = 0 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <ci>Vbar_cGMP</ci> <ci>V_cGMP</ci> </apply> <ci>tau_sGC</ci> </apply> </math> V_cGMP:time = (Vbar_cGMP-V_cGMP)/tau_sGC Maximal reaction velocity of cyclic GMP formation <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1.26E-7</cn> </math> V_cGMPmax = 1.26E-7 V_m0 Vascular smooth muscle cell plasma membrane potential false Rate of change of vascular smooth muscle cell plasma membrane potential <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <cn>1</cn> <ci>C_m</ci> </apply> <apply> <plus /> <apply> <times /> <apply> <plus /> <apply> <plus /> <apply> <plus /> <apply> <plus /> <apply> <plus /> <apply> <plus /> <apply> <plus /> <apply> <plus /> <apply> <plus /> <ci>I_VOCC</ci> <ci>I_BKCa</ci> </apply> <ci>I_Kv</ci> </apply> <ci>I_Kleak</ci> </apply> <ci>I_NSC</ci> </apply> <ci>I_SOC</ci> </apply> <ci>I_ClCa</ci> </apply> <ci>I_PMCA</ci> </apply> <ci>I_NCX</ci> </apply> <ci>I_NaK</ci> </apply> <cn>-1</cn> </apply> <ci>I_stim</ci> </apply> </apply> </math> V_m:time = 1/C_m*((I_VOCC+I_BKCa+I_Kv+I_Kleak+I_NSC+I_SOC+I_ClCa+I_PMCA+I_NCX+I_NaK)*(-1)+I_stim) Initial vascular smooth muscle cell plasma membrane potential <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>-59.4</cn> </math> V_m0 = -59.4 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <cn>1</cn> <ci>C_m</ci> </apply> <apply> <plus /> <apply> <times /> <apply> <plus /> <apply> <plus /> <apply> <plus /> <apply> <plus /> <apply> <plus /> <apply> <plus /> <apply> <plus /> <apply> <plus /> <apply> <plus /> <ci>I_VOCC</ci> <ci>I_BKCa</ci> </apply> <ci>I_Kv</ci> </apply> <ci>I_Kleak</ci> </apply> <ci>I_NSC</ci> </apply> <ci>I_SOC</ci> </apply> <ci>I_ClCa</ci> </apply> <ci>I_PMCA</ci> </apply> <ci>I_NCX</ci> </apply> <ci>I_NaK</ci> </apply> <cn>-1</cn> </apply> <ci>I_stim</ci> </apply> </apply> </math> V_m:time = 1/C_m*((I_VOCC+I_BKCa+I_Kv+I_Kleak+I_NSC+I_SOC+I_ClCa+I_PMCA+I_NCX+I_NaK)*(-1)+I_stim) Electrical potential http://bhi.washington.edu/OPB#OPB_00506 Steady state velocity of cyclic GMP formation <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <times /> <ci>V_cGMPmax</ci> <apply> <plus /> <apply> <times /> <ci>B5_sGC</ci> <ci>NO</ci> </apply> <apply> <power /> <ci>NO</ci> <cn>2</cn> </apply> </apply> </apply> <apply> <plus /> <apply> <plus /> <ci>A0_sGC</ci> <apply> <times /> <ci>A1_sGC</ci> <ci>NO</ci> </apply> </apply> <apply> <power /> <ci>NO</ci> <cn>2</cn> </apply> </apply> </apply> </math> Vbar_cGMP = V_cGMPmax*(B5_sGC*NO+NO^2)/(A0_sGC+A1_sGC*NO+NO^2) Cytosolic volume available to calcium <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.7</cn> </math> Vol_Ca = .7 Fluid volume http://bhi.washington.edu/OPB#OPB_01061 Sarcoplasmic reticulum volume associated with the ryanodine receptor release which is also called the terminal cisternae <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.007</cn> </math> Vol_SRr = .007 Fluid volume http://bhi.washington.edu/OPB#OPB_01061 Sarcoplasmic reticulum volume associated with the SERCA uptake <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.07</cn> </math> Vol_SRu = .07 Fluid volume http://bhi.washington.edu/OPB#OPB_01061 Total cytosolic volume <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1</cn> </math> Vol_i = 1 Fluid volume http://bhi.washington.edu/OPB#OPB_01061 Voltage gated potassium channel current Total cell voltage gated potassium channel current 1.0 1.0 Ca-act Cl channel cGMP sensitivity term <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <power /> <apply> <divide /> <ci>cGMP_i</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">1</cn> </apply> <ci>n_ClcGMP</ci> </apply> <apply> <plus /> <apply> <power /> <apply> <divide /> <ci>cGMP_i</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">1</cn> </apply> <ci>n_ClcGMP</ci> </apply> <apply> <power /> <apply> <times /> <apply> <divide /> <ci>K_ClcGMP</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM">1</cn> </apply> <cn>.001</cn> </apply> <ci>n_ClcGMP</ci> </apply> </apply> </apply> </math> alpha_Cl = (cGMP_i/1)^n_ClcGMP/((cGMP_i/1)^n_ClcGMP+(K_ClcGMP/1*.001)^n_ClcGMP) Alpha adrenoceptor G protein effective signal gain parameter <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>2.781E-8</cn> </math> alpha_G = 2.781E-8 cGMP_i0 Intracellular cGMP concentration false Rate of change of intracellular cGMP concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <minus /> <ci>V_cGMP</ci> <apply> <times /> <ci>k_pdecGMP</ci> <apply> <divide /> <apply> <power /> <ci>cGMP_i</ci> <cn>2</cn> </apply> <apply> <plus /> <ci>cGMP_i</ci> <ci>K_mpde</ci> </apply> </apply> </apply> </apply> </math> cGMP_i:time = V_cGMP-k_pdecGMP*(cGMP_i^2/(cGMP_i+K_mpde)) Initial intracellular cGMP concentration <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>0</cn> </math> cGMP_i0 = 0 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <minus /> <ci>V_cGMP</ci> <apply> <times /> <ci>k_pdecGMP</ci> <apply> <divide /> <apply> <power /> <ci>cGMP_i</ci> <cn>2</cn> </apply> <apply> <plus /> <ci>cGMP_i</ci> <ci>K_mpde</ci> </apply> </apply> </apply> </apply> </math> cGMP_i:time = V_cGMP-k_pdecGMP*(cGMP_i^2/(cGMP_i+K_mpde)) Chemical concentration http://bhi.washington.edu/OPB#OPB_00340 Large conductance calcium activated potassium channel maximal NO independent voltage shift at 50% response <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>46.3</cn> </math> dV_50KCaNO = 46.3 Large conductance calcium activated potassium channel maximal cGMP independent voltage shift at 50% response <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>76</cn> </math> dV_50KCacGMP = 76 d_L0 L-type calcium channel activation gate probability false Rate of change of L-type calcium channel activation gate probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <ci>dbar_L</ci> <ci>d_L</ci> </apply> <ci>tau_dL</ci> </apply> </math> d_L:time = (dbar_L-d_L)/tau_dL Initial L-type calcium channel activation gate probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <cn>1</cn> <apply> <plus /> <cn>1</cn> <apply> <exp /> <apply> <times /> <apply> <divide /> <ci>V_m0</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">8.3</cn> </apply> <cn>-1</cn> </apply> </apply> </apply> </apply> </math> d_L0 = 1/(1+exp(V_m0/8.3*(-1))) <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <ci>dbar_L</ci> <ci>d_L</ci> </apply> <ci>tau_dL</ci> </apply> </math> d_L:time = (dbar_L-d_L)/tau_dL Sodium-calcium exchanger sensitivity factor <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>3E-4</cn> </math> d_NCX = 3E-4 Minimal NSC channel activation <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.0244</cn> </math> d_NSCmin = .0244 Voltage operated calcium channel d gate steady state open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <cn>1</cn> <apply> <plus /> <cn>1</cn> <apply> <exp /> <apply> <times /> <apply> <divide /> <ci>V_m</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">8.3</cn> </apply> <cn>-1</cn> </apply> </apply> </apply> </apply> </math> dbar_L = 1/(1+exp(V_m/8.3*(-1))) Alpha adrentoceptor tatio of activated unbound ligand <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <times /> <ci>k_dG</ci> <ci>G_0</ci> </apply> <apply> <times /> <ci>k_aG</ci> <apply> <minus /> <ci>G_TG</ci> <ci>G_0</ci> </apply> </apply> </apply> </math> deltaG_0 = k_dG*G_0/(k_aG*(G_TG-G_0)) f_L0 L-type calcium channel inactivation gate open probability false Rate of change of L-type calcium channel inactivation gate open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <ci>fbar_L</ci> <ci>f_L</ci> </apply> <ci>tau_fL</ci> </apply> </math> f_L:time = (fbar_L-f_L)/tau_fL Initial L-type calcium channel inactivation gate open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <cn>1</cn> <apply> <plus /> <cn>1</cn> <apply> <exp /> <apply> <divide /> <apply> <plus /> <ci>V_m0</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">42</cn> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">9.1</cn> </apply> </apply> </apply> </apply> </math> f_L0 = 1/(1+exp((V_m0+42)/9.1)) <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <ci>fbar_L</ci> <ci>f_L</ci> </apply> <ci>tau_fL</ci> </apply> </math> f_L:time = (fbar_L-f_L)/tau_fL Steady state L-type calcium channel inactivation gate open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <cn>1</cn> <apply> <plus /> <cn>1</cn> <apply> <exp /> <apply> <divide /> <apply> <plus /> <ci>V_m</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">42</cn> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">9.1</cn> </apply> </apply> </apply> </apply> </math> fbar_L = 1/(1+exp((V_m+42)/9.1)) Vascular smooth muscle cell http://purl.org/sig/ont/fma/fma284560 Vascular smooth muscle cell http://purl.org/sig/ont/fma/fma284560 Plasma membrane http://purl.org/sig/ont/fma/fma63841 Portion of cytosol http://purl.org/sig/ont/fma/fma66836 Matrix of endoplasmic reticulum cistern http://purl.org/sig/ont/fma/fma67120 Matrix of endoplasmic reticulum cistern http://purl.org/sig/ont/fma/fma67120 Sarcoplasmic reticulum http://purl.org/sig/ont/fma/fma67225 Matrix of endoplasmic reticulum http://purl.org/sig/ont/fma/fma72448 Matrix of endoplasmic reticulum http://purl.org/sig/ont/fma/fma72448 Portion of extracellular matrix http://purl.org/sig/ont/fma/fma9672 Store operated cation channel maximal calcium conductance <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.0083</cn> </math> gCa_SOC = .0083 Electrical conductance http://bhi.washington.edu/OPB#OPB_00015 Store operated cation channel maximal sodium conductance <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.0575</cn> </math> gNa_SOC = .0575 Electrical conductance http://bhi.washington.edu/OPB#OPB_00015 Calcium activated chloride channel maximal conductance <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.23</cn> </math> g_ClCa = .23 Electrical conductance http://bhi.washington.edu/OPB#OPB_00015 Potassium leak channel maximal conductance <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.067</cn> </math> g_Kleak = .067 Electrical conductance http://bhi.washington.edu/OPB#OPB_00015 Voltage gated potassium channel maximal conductance <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1.35</cn> </math> g_Kv = 1.35 Electrical conductance http://bhi.washington.edu/OPB#OPB_00015 Sodium/calcium exchanger current factor <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>4.87E-4</cn> </math> g_NCX = 4.87E-4 PIP2 particle number to concentration conversion term <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <ci>N_Avo</ci> <ci>Vol_i</ci> </apply> </math> gamma_G = N_Avo*Vol_i Sodium/calcium exchanger parameter <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.45</cn> </math> gamma_NCX = .45 h_IP30 IP3 receptor activation gate open probability false Rate of change of IP3 receptor activation gate open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <ci>k_onIP3</ci> <apply> <minus /> <ci>K_inhIP3</ci> <apply> <times /> <apply> <plus /> <ci>Ca_i</ci> <ci>K_inhIP3</ci> </apply> <ci>h_IP3</ci> </apply> </apply> </apply> </math> h_IP3:time = k_onIP3*(K_inhIP3-(Ca_i+K_inhIP3)*h_IP3) Initial IP3 receptor activation gate open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <ci>K_inhIP3</ci> <apply> <plus /> <ci>Ca_i0</ci> <ci>K_inhIP3</ci> </apply> </apply> </math> h_IP30 = K_inhIP3/(Ca_i0+K_inhIP3) <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <ci>k_onIP3</ci> <apply> <minus /> <ci>K_inhIP3</ci> <apply> <times /> <apply> <plus /> <ci>Ca_i</ci> <ci>K_inhIP3</ci> </apply> <ci>h_IP3</ci> </apply> </apply> </apply> </math> h_IP3:time = k_onIP3*(K_inhIP3-(Ca_i+K_inhIP3)*h_IP3) Single channel large conductance calcium activated potassium channel current <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <divide /> <apply> <times /> <apply> <times /> <apply> <times /> <apply> <times /> <ci>P_BKCa</ci> <ci>V_m</ci> </apply> <ci>F</ci> </apply> <ci>FRT</ci> </apply> <apply> <minus /> <ci>K_e</ci> <apply> <times /> <ci>K_i</ci> <apply> <exp /> <apply> <times /> <ci>V_m</ci> <ci>FRT</ci> </apply> </apply> </apply> </apply> </apply> <apply> <minus /> <cn>1</cn> <apply> <exp /> <apply> <times /> <ci>V_m</ci> <ci>FRT</ci> </apply> </apply> </apply> </apply> <cn>1E6</cn> </apply> </math> i_KCa = P_BKCa*V_m*F*FRT*(K_e-K_i*exp(V_m*FRT))/(1-exp(V_m*FRT))*1E6 Soluble guanylate cyclase activation and cyclic GMP formation rate constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>2E3</cn> </math> k_1sGC = 2E3 Soluble guanylate cyclase activation and cyclic GMP formation rate constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>6.4E-6</cn> </math> k_2sGC = 6.4E-6 Soluble guanylate cyclase activation and cyclic GMP formation rate constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>4.2</cn> </math> k_3sGC = 4.2 Soluble guanylate cyclase activation and cyclic GMP formation parameter <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1E-4</cn> </math> k_DrsGC = 1E-4 Soluble guanylate cyclase activation and cyclic GMP formation rate constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>4E-4</cn> </math> k_DsGC = 4E-4 G protein activation rate <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1.7E-4</cn> </math> k_aG = 1.7E-4 G protein deactivation rate <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.0015</cn> </math> k_dG = .0015 IP3 degradation rate <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.00125</cn> </math> k_degG = .00125 Alpha adrenoceptor endocytosis rate <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>6E-6</cn> </math> k_eG = 6E-6 Soluble guanylate cyclase activation and cyclic GMP formation rate constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.015</cn> </math> k_m1sGC = .015 Soluble guanylate cyclase activation and cyclic GMP formation rate constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1E-7</cn> </math> k_m2sGC = 1E-7 IP3 receptor rate of calcium binding to inhibition site <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1.4</cn> </math> k_onIP3 = 1.4 Alpha adrenoceptor phosphorylation rate <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1E-4</cn> </math> k_pG = 1E-4 Soluble guanylate cyclase activation and cyclic GMP formation rate constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>6.95E-5</cn> </math> k_pdecGMP = 6.95E-5 Alpha adrenoceptor recycling rate <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1.75E-7</cn> </math> k_rG = 1.75E-7 Calcium activated chloride channel calcium sensitivity Hill coefficient <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>2</cn> </math> n_ClCa = 2 Calcium activated chloride channel cyclic GMP sensitivity Hill coefficient <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>3.3</cn> </math> n_ClcGMP = 3.3 Sodium/potassium ATPase extracellular potassium Hill coefficient <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1.1</cn> </math> n_HKe = 1.1 Sodium/potassium ATPase intracellular sodium Hill coefficient <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1.7</cn> </math> n_HNai = 1.7 p_K0 Voltage gated potassium channel activation gate open probability false Rate of change of voltage gated potassium channel activation gate open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <ci>pbar_K</ci> <ci>p_K</ci> </apply> <ci>tau_pK</ci> </apply> </math> p_K:time = (pbar_K-p_K)/tau_pK Initial voltage gated potassium channel activation gate open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <cn>1</cn> <apply> <plus /> <cn>1</cn> <apply> <exp /> <apply> <times /> <apply> <divide /> <apply> <plus /> <ci>V_m0</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">11</cn> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">15</cn> </apply> <cn>-1</cn> </apply> </apply> </apply> </apply> </math> p_K0 = 1/(1+exp((V_m0+11)/15*(-1))) <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <ci>pbar_K</ci> <ci>p_K</ci> </apply> <ci>tau_pK</ci> </apply> </math> p_K:time = (pbar_K-p_K)/tau_pK p_f0 Large conductance calcium activated potassium channel fast activation gate open probability false Rate of change of large conductance calcium activated potassium channel fast activation gate open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <ci>pbar_o</ci> <ci>p_f</ci> </apply> <ci>tau_pf</ci> </apply> </math> p_f:time = (pbar_o-p_f)/tau_pf Initial large conductance calcium activated potassium channel fast activation gate open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <cn>1</cn> <apply> <plus /> <cn>1</cn> <apply> <exp /> <apply> <times /> <apply> <divide /> <apply> <minus /> <ci>V_m0</ci> <ci>V_50KCa0</ci> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">18.25</cn> </apply> <cn>-1</cn> </apply> </apply> </apply> </apply> </math> p_f0 = 1/(1+exp((V_m0-V_50KCa0)/18.25*(-1))) <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <ci>pbar_o</ci> <ci>p_f</ci> </apply> <ci>tau_pf</ci> </apply> </math> p_f:time = (pbar_o-p_f)/tau_pf p_s0 Large conductance calcium activated potassium channel slow activation gate open probability false Rate of change of large conductance calcium activated potassium channel slow activation gate open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <ci>pbar_o</ci> <ci>p_s</ci> </apply> <ci>tau_ps</ci> </apply> </math> p_s:time = (pbar_o-p_s)/tau_ps Initial large conductance calcium activated potassium channel slow activation gate open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <cn>1</cn> <apply> <plus /> <cn>1</cn> <apply> <exp /> <apply> <times /> <apply> <divide /> <apply> <minus /> <ci>V_m0</ci> <ci>V_50KCa0</ci> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">18.25</cn> </apply> <cn>-1</cn> </apply> </apply> </apply> </apply> </math> p_s0 = 1/(1+exp((V_m0-V_50KCa0)/18.25*(-1))) <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <ci>pbar_o</ci> <ci>p_s</ci> </apply> <ci>tau_ps</ci> </apply> </math> p_s:time = (pbar_o-p_s)/tau_ps Voltage gated potassium channel activation gate steady state open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <cn>1</cn> <apply> <plus /> <cn>1</cn> <apply> <exp /> <apply> <times /> <apply> <divide /> <apply> <plus /> <ci>V_m</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">11</cn> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">15</cn> </apply> <cn>-1</cn> </apply> </apply> </apply> </apply> </math> pbar_K = 1/(1+exp((V_m+11)/15*(-1))) Voltage gated potassium channel fast and slow activation gate steady state open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <cn>1</cn> <apply> <plus /> <cn>1</cn> <apply> <exp /> <apply> <times /> <apply> <divide /> <apply> <minus /> <ci>V_m</ci> <ci>V_50KCa</ci> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">18.25</cn> </apply> <cn>-1</cn> </apply> </apply> </apply> </apply> </math> pbar_o = 1/(1+exp((V_m-V_50KCa)/18.25*(-1))) Sodium/calcium exchanger forward reaction rate <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <exp /> <apply> <times /> <apply> <times /> <ci>gamma_NCX</ci> <ci>V_m</ci> </apply> <ci>FRT</ci> </apply> </apply> </math> phi_F = exp(gamma_NCX*V_m*FRT) Sodium/calcium exchanger reverse reaction rate <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <exp /> <apply> <times /> <apply> <times /> <apply> <minus /> <ci>gamma_NCX</ci> <cn>1</cn> </apply> <ci>V_m</ci> </apply> <ci>FRT</ci> </apply> </apply> </math> phi_R = exp((gamma_NCX-1)*V_m*FRT) q_10 Voltage gated potassium channel fast activation gate open probability false Rate of change of voltage gated potassium channel fast activation gate open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <ci>qbar</ci> <ci>q_1</ci> </apply> <ci>tau_q1</ci> </apply> </math> q_1:time = (qbar-q_1)/tau_q1 Initial voltage gated potassium channel fast activation gate open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <cn>1</cn> <apply> <plus /> <cn>1</cn> <apply> <exp /> <apply> <divide /> <apply> <plus /> <ci>V_m0</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">40</cn> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">14</cn> </apply> </apply> </apply> </apply> </math> q_10 = 1/(1+exp((V_m0+40)/14)) <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <ci>qbar</ci> <ci>q_1</ci> </apply> <ci>tau_q1</ci> </apply> </math> q_1:time = (qbar-q_1)/tau_q1 q_20 Voltage gated potassium channel slow activation gate open probability false Rate of change of voltage gated potassium channel slow activation gate open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <ci>qbar</ci> <ci>q_2</ci> </apply> <ci>tau_q2</ci> </apply> </math> q_2:time = (qbar-q_2)/tau_q2 Initial voltage gated potassium channel slow activation gate open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <cn>1</cn> <apply> <plus /> <cn>1</cn> <apply> <exp /> <apply> <divide /> <apply> <plus /> <ci>V_m0</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">40</cn> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">14</cn> </apply> </apply> </apply> </apply> </math> q_20 = 1/(1+exp((V_m0+40)/14)) <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <minus /> <ci>qbar</ci> <ci>q_2</ci> </apply> <ci>tau_q2</ci> </apply> </math> q_2:time = (qbar-q_2)/tau_q2 Voltage gated potassium channel fast and slow activation gate steady state open probability <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <cn>1</cn> <apply> <plus /> <cn>1</cn> <apply> <exp /> <apply> <divide /> <apply> <plus /> <ci>V_m</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">40</cn> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">14</cn> </apply> </apply> </apply> </apply> </math> qbar = 1/(1+exp((V_m+40)/14)) Inositol trisphosphate and PIP2 baseline production rate factor Iniital inositol trisphosphate and PIP2 baseline production rate factor <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <times /> <apply> <times /> <ci>k_degG</ci> <ci>gamma_G</ci> </apply> <ci>IP3_0</ci> </apply> <ci>PIP2_0</ci> </apply> </math> r_hG0 = k_degG*gamma_G*IP3_0/PIP2_0 <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <apply> <times /> <ci>alpha_G</ci> <apply> <divide /> <ci>Ca_i</ci> <apply> <plus /> <ci>Ca_i</ci> <ci>K_cG</ci> </apply> </apply> </apply> <ci>G</ci> </apply> </math> r_hG = alpha_G*(Ca_i/(Ca_i+K_cG))*G PIP2 baseline production rate <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1.5E-5</cn> </math> r_rG = 1.5E-5 Alpha adrenoceptors norepinephrine sensitivity factor <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <divide /> <apply> <times /> <ci>NE</ci> <ci>R_supSG</ci> </apply> <apply> <times /> <apply> <times /> <ci>xi_G</ci> <ci>R_TG</ci> </apply> <apply> <plus /> <ci>K_1G</ci> <ci>NE</ci> </apply> </apply> </apply> </math> rho_rG = NE*R_supSG/(xi_G*R_TG*(K_1G+NE)) Store operated cation channel activaton gate time constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>100</cn> </math> tau_SOC = 100 L-type calcium channel d_L gate time constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <plus /> <apply> <times /> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="ms">2.5</cn> <apply> <exp /> <apply> <times /> <apply> <power /> <apply> <divide /> <apply> <plus /> <ci>V_m</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">40</cn> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">30</cn> </apply> <cn>2</cn> </apply> <cn>-1</cn> </apply> </apply> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="ms">1.15</cn> </apply> </math> tau_dL = 2.5*exp(((V_m+40)/30)^2*(-1))+1.15 L-type calcium channel f_L gate time constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <plus /> <apply> <times /> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="ms">65</cn> <apply> <exp /> <apply> <times /> <apply> <power /> <apply> <divide /> <apply> <plus /> <ci>V_m</ci> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">35</cn> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mV">25</cn> </apply> <cn>2</cn> </apply> <cn>-1</cn> </apply> </apply> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="ms">45</cn> </apply> </math> tau_fL = 65*exp(((V_m+35)/25)^2*(-1))+45 Voltage gated potassium channel activaton gate time constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <apply> <times /> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="ms">61.49</cn> <apply> <exp /> <apply> <times /> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="1/mV">-0.0268</cn> <ci>V_m</ci> </apply> </apply> </apply> </math> tau_pK = 61.49*exp((-0.0268)*V_m) Large conductance calcium activated potassium channel fast activaton gate time constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.84</cn> </math> tau_pf = .84 Large conductance calcium activated potassium channel slow activaton gate time constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>35.9</cn> </math> tau_ps = 35.9 Voltage gated potassium channel fast inactivaton gate time constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>371</cn> </math> tau_q1 = 371 Voltage gated potassium channel slow inactivaton gate time constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>2884</cn> </math> tau_q2 = 2884 Ryanodine receptor calcium release time constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.0333</cn> </math> tau_rel = .0333 cyclic GMP rate of the reaction velocity time constant <math xmlns="http://www.w3.org/1998/Math/MathML"> <piecewise> <piece> <apply> <divide /> <cn>1</cn> <apply> <plus /> <apply> <times /> <ci>k_3sGC</ci> <ci>NO</ci> </apply> <ci>k_DrsGC</ci> </apply> </apply> <apply> <or /> <apply> <eq /> <apply> <minus /> <ci>Vbar_cGMP</ci> <ci>V_cGMP</ci> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM/ms">0</cn> </apply> <apply> <gt /> <apply> <minus /> <ci>Vbar_cGMP</ci> <ci>V_cGMP</ci> </apply> <cn xmlns:xmml="http://www.physiome.org/jsim/standard/xmml/2.01" xmml:units="mM/ms">0</cn> </apply> </apply> </piece> <otherwise> <apply> <divide /> <cn>1</cn> <apply> <plus /> <ci>k_m2sGC</ci> <ci>k_DrsGC</ci> </apply> </apply> </otherwise> </piecewise> </math> tau_sGC = if (((Vbar_cGMP-V_cGMP)=0) or ((Vbar_cGMP-V_cGMP)>0)) 1/(k_3sGC*NO+k_DrsGC) else 1/(k_m2sGC+k_DrsGC) Sarcoplasmic reticulum internal rate of diffusion of calcium between uptake an release compartments <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1E3</cn> </math> tau_tr = 1E3 Time http://bhi.washington.edu/OPB#OPB_01023 true Time Integration time step <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.5</cn> </math> time.delta = .5 Simulation end time <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>2E5</cn> </math> time.max = 2E5 Simulation start time <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>0</cn> </math> time.min = 0 Alpha adrnoceptor Fraction that are mobile <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>.85</cn> </math> xi_G = .85 Valence of calcium <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>2</cn> </math> z_Ca = 2 Valence of chloride <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>-1</cn> </math> z_Cl = -1 Valence of potassium <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1</cn> </math> z_K = 1 Valence of sodium <math xmlns="http://www.w3.org/1998/Math/MathML"> <cn>1</cn> </math> z_Na = 1