<?xml version='1.0' encoding='UTF-8'?>
<model cmeta:id="saucerman_brunton_michailova_mcculloch_2003" name="saucerman_brunton_michailova_mcculloch_2003" xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
<units name="mM">
<unit prefix="milli" units="mole"/>
<unit exponent="-1" units="litre"/>
</units>
<units name="per_mM4">
<unit exponent="-4" units="mM"/>
</units>
<units name="uM">
<unit prefix="micro" units="mole"/>
<unit exponent="-1" units="litre"/>
</units>
<units name="m_to_u">
<unit units="uM"/>
<unit exponent="-1" units="mM"/>
</units>
<units name="per_sec">
<unit exponent="-1" units="second"/>
</units>
<units name="ms">
<unit prefix="3" units="second"/>
</units>
<units name="mM_per_sec">
<unit units="mM"/>
<unit exponent="-1" units="second"/>
</units>
<units name="uM_per_sec">
<unit units="uM"/>
<unit exponent="-1" units="second"/>
</units>
<units name="per_mM_per_sec">
<unit exponent="-1" units="mM"/>
<unit exponent="-1" units="second"/>
</units>
<units name="per_uM_per_sec">
<unit exponent="-1" units="uM"/>
<unit exponent="-1" units="second"/>
</units>
<units name="uL">
<unit prefix="micro" units="litre"/>
</units>
<units name="pL">
<unit prefix="pico" units="litre"/>
</units>
<units name="cm_per_sec">
<unit prefix="centi" units="metre"/>
<unit exponent="-1" units="second"/>
</units>
<units name="cm2">
<unit exponent="2" prefix="centi" units="metre"/>
</units>
<units name="mV">
<unit prefix="milli" units="volt"/>
</units>
<units name="per_mV">
<unit exponent="-1" units="mV"/>
</units>
<units name="per_mV_per_second">
<unit units="per_mV"/>
<unit exponent="-1" units="second"/>
</units>
<units name="mV_per_sec">
<unit prefix="milli" units="volt"/>
<unit exponent="-1" units="second"/>
</units>
<units name="mS_per_uF">
<unit prefix="milli" units="siemens"/>
<unit exponent="-1" prefix="micro" units="farad"/>
</units>
<units name="uA_per_uF">
<unit prefix="micro" units="ampere"/>
<unit exponent="-1" prefix="micro" units="farad"/>
</units>
<units name="joules_per_kmole_kelvin">
<unit units="joule"/>
<unit exponent="-3" units="mole"/>
<unit exponent="-1" units="kelvin"/>
</units>
<units name="ng">
<unit prefix="nano" units="gram"/>
</units>
<units name="coulombs_per_mole">
<unit units="coulomb"/>
<unit exponent="-1" units="mole"/>
</units>
<units name="pmol_per_mg">
<unit prefix="pico" units="mole"/>
<unit exponent="-1" prefix="milli" units="gram"/>
</units>
<units name="uM_to_pmol_per_mg">
<unit units="pmol_per_mg"/>
<unit exponent="-1" units="uM"/>
</units>
<units name="nFC_per_sAcm2">
<unit prefix="nano" units="farad"/>
<unit units="coulomb"/>
<unit exponent="-1" units="second"/>
<unit exponent="-1" units="ampere"/>
<unit exponent="-2" prefix="centi" units="metre"/>
</units>
<units name="ibar_to_I">
<unit units="ampere"/>
<unit units="second"/>
<unit units="litre"/>
<unit exponent="-1" units="farad"/>
<unit exponent="-1" units="metre"/>
<unit exponent="-1" units="coulomb"/>
</units>
<component name="environment">
<variable name="time" public_interface="out" units="second"/>
<!--protocol:
0 - none
1 - current injection at Ipace
2 - Voltage clamp-->
<variable initial_value="1" name="protocol" public_interface="out" units="dimensionless"/>
</component>
<component name="b1_AR_Gs_parameters">
<variable initial_value="0.01" name="L_totmax" public_interface="out" units="uM"/>
<variable initial_value="0.0132" name="sum_b1_AR" public_interface="out" units="uM"/>
<variable initial_value="3.83" name="Gs_tot" public_interface="out" units="uM"/>
<variable initial_value="0.285" name="Kl" public_interface="out" units="uM"/>
<variable initial_value="0.062" name="Kr" public_interface="out" units="uM"/>
<variable initial_value="33" name="Kc" public_interface="out" units="uM"/>
<variable initial_value="1.1e-3" name="k_bar_kp" public_interface="out" units="per_sec"/>
<variable initial_value="2.2e-3" name="k_bar_km" public_interface="out" units="per_sec"/>
<variable initial_value="3.6e-3" name="k_p_kap" public_interface="out" units="per_uM_per_sec"/>
<variable initial_value="2.2e-3" name="k_p_kam" public_interface="out" units="per_sec"/>
<variable initial_value="16" name="k_g_act" public_interface="out" units="per_sec"/>
<variable initial_value="0.8" name="k_hyd" public_interface="out" units="per_sec"/>
<variable initial_value="1.21e3" name="k_reassoc" public_interface="out" units="per_uM_per_sec"/>
</component>
<component name="cAMP_parameters">
<variable initial_value="49.7e-3" name="AC_tot" public_interface="out" units="uM"/>
<variable initial_value="5e3" name="ATP" public_interface="out" units="uM"/>
<variable initial_value="38.9e-3" name="PDE_tot" public_interface="out" units="uM"/>
<variable initial_value="0" name="IBMX_tot" public_interface="out" units="uM"/>
<variable initial_value="0" name="Fsk_tot" public_interface="out" units="uM"/>
<variable initial_value="0.2" name="k_ac_basal" public_interface="out" units="per_sec"/>
<variable initial_value="8.5" name="k_ac_gsa" public_interface="out" units="per_sec"/>
<variable initial_value="7.3" name="k_ac_fsk" public_interface="out" units="per_sec"/>
<variable initial_value="5" name="k_pde" public_interface="out" units="per_sec"/>
<variable initial_value="1.03e3" name="Km_basal" public_interface="out" units="uM"/>
<variable initial_value="315" name="Km_gsa" public_interface="out" units="uM"/>
<variable initial_value="860" name="Km_fsk" public_interface="out" units="uM"/>
<variable initial_value="1.3" name="Km_pde" public_interface="out" units="uM"/>
<variable initial_value="0.4" name="K_gsa" public_interface="out" units="uM"/>
<variable initial_value="44" name="K_fsk" public_interface="out" units="uM"/>
<variable initial_value="30" name="Ki_ibmx" public_interface="out" units="uM"/>
</component>
<component name="PKA_parameters">
<variable initial_value="0.59" name="PKAI_tot" public_interface="out" units="uM"/>
<variable initial_value="0.025" name="PKAII_tot" public_interface="out" units="uM"/>
<variable initial_value="0.18" name="PKI_tot" public_interface="out" units="uM"/>
<variable initial_value="9.14" name="K_a" public_interface="out" units="uM"/>
<variable initial_value="1.64" name="K_b" public_interface="out" units="uM"/>
<variable initial_value="4.375" name="K_d" public_interface="out" units="uM"/>
<variable initial_value="0.2e-3" name="Ki_pki" public_interface="out" units="uM"/>
</component>
<component name="PLB_parameters">
<variable initial_value="106" name="PLB_tot" public_interface="out" units="uM"/>
<variable initial_value="0.89" name="PP1_tot" public_interface="out" units="uM"/>
<variable initial_value="0.3" name="Inhib1_tot" public_interface="out" units="uM"/>
<variable initial_value="54" name="k_pka_plb" public_interface="out" units="per_sec"/>
<variable initial_value="21" name="Km_pka_plb" public_interface="out" units="uM"/>
<variable initial_value="8.5" name="k_pp1_plb" public_interface="out" units="per_sec"/>
<variable initial_value="7" name="Km_pp1_plb" public_interface="out" units="uM"/>
<variable initial_value="60" name="k_pka_i1" public_interface="out" units="per_sec"/>
<variable initial_value="1" name="Km_pka_i1" public_interface="out" units="uM"/>
<variable initial_value="14" name="Vmax_pp2a_i1" public_interface="out" units="uM_per_sec"/>
<variable initial_value="1" name="Km_pp2a_i1" public_interface="out" units="uM"/>
<variable initial_value="1e-3" name="Ki_inhib1" public_interface="out" units="uM"/>
</component>
<component name="LCC_parameters">
<variable initial_value="10" name="epsilon" public_interface="out" units="dimensionless"/>
<variable initial_value="25e-3" name="LCC_tot" public_interface="out" units="uM"/>
<variable initial_value="25e-3" name="PP1_lcc_tot" public_interface="out" units="uM"/>
<variable initial_value="25e-3" name="PP2A_lcc_tot" public_interface="out" units="uM"/>
<variable initial_value="54" name="k_pka_lcc" public_interface="out" units="per_sec"/>
<variable initial_value="21" name="Km_pka_lcc" public_interface="out" units="uM"/>
<variable initial_value="8.52" name="k_pp1_lcc" public_interface="out" units="per_sec"/>
<variable initial_value="3" name="Km_pp1_lcc" public_interface="out" units="uM"/>
<variable initial_value="10.1" name="k_pp2a_lcc" public_interface="out" units="per_sec"/>
<variable initial_value="3" name="Km_pp2a_lcc" public_interface="out" units="uM"/>
</component>
<component name="EC_Coupling_Parameters">
<variable initial_value="20.8e-6" name="V_myo" public_interface="out" units="uL"/>
<variable initial_value="9.88e-7" name="V_nsr" public_interface="out" units="uL"/>
<variable initial_value="9.3e-8" name="V_jsr" public_interface="out" units="uL"/>
<variable initial_value="1.534e-4" name="A_Cap" public_interface="out" units="cm2"/>
<variable initial_value="310" name="Temp" public_interface="out" units="kelvin"/>
<variable initial_value="140" name="Na_ext" public_interface="out" units="mM"/>
<variable initial_value="5.4" name="K_ext" public_interface="out" units="mM"/>
<variable initial_value="1.8" name="Ca_ext" public_interface="out" units="mM"/>
<variable initial_value="8" name="G_Na" public_interface="out" units="mS_per_uF"/>
<variable initial_value="0.35" name="G_to" public_interface="out" units="mS_per_uF"/>
<variable initial_value="0.07" name="G_ss" public_interface="out" units="mS_per_uF"/>
<variable initial_value="0.24" name="G_Ki_bar" public_interface="out" units="mS_per_uF"/>
<variable initial_value="0.008" name="G_Kp" public_interface="out" units="mS_per_uF"/>
<variable initial_value="300" name="f" public_interface="out" units="per_sec"/>
<variable initial_value="2e3" name="g" public_interface="out" units="per_sec"/>
<variable initial_value="5187.5" name="gamma_o" public_interface="out" units="per_mM_per_sec"/>
<variable initial_value="10" name="omega" public_interface="out" units="per_sec"/>
<variable initial_value="1.7469e-8" name="p_Ca" public_interface="out" units="cm_per_sec"/>
<variable initial_value="3.234e-11" name="p_K" public_interface="out" units="cm_per_sec"/>
<variable initial_value="3e5" name="N_lcc" public_interface="out" units="dimensionless"/>
<variable initial_value="-0.458" name="I_Ca05" public_interface="out" units="uA_per_uF"/>
<variable initial_value="1483" name="k_NaCa" public_interface="out" units="uA_per_uF"/>
<variable initial_value="87.5" name="Km_Na" public_interface="out" units="mM"/>
<variable initial_value="1.38" name="Km_Ca" public_interface="out" units="mM"/>
<variable initial_value="0.1" name="k_sat" public_interface="out" units="dimensionless"/>
<variable initial_value="0.35" name="eta" public_interface="out" units="dimensionless"/>
<variable initial_value="1.1" name="I_bar_NaK" public_interface="out" units="uA_per_uF"/>
<variable initial_value="10" name="Km_Nai" public_interface="out" units="mM"/>
<variable initial_value="1.5" name="Km_Ko" public_interface="out" units="mM"/>
<variable initial_value="1.15" name="I_bar_PCa" public_interface="out" units="uA_per_uF"/>
<variable initial_value="0.5e-3" name="Km_PCa" public_interface="out" units="mM"/>
<variable initial_value="2.8e-3" name="G_CaB" public_interface="out" units="uA_per_uF"/>
<variable initial_value="1.18e-3" name="G_NaB" public_interface="out" units="uA_per_uF"/>
<variable initial_value="0" name="Pns" public_interface="out" units="dimensionless"/>
<variable initial_value="1.2e-3" name="Km_NS" public_interface="out" units="mM"/>
<variable initial_value="4.7" name="I_up_bar" public_interface="out" units="mM_per_sec"/>
<variable initial_value="3e-4" name="Km_up0" public_interface="out" units="mM"/>
<variable initial_value="15" name="NSR_bar" public_interface="out" units="mM"/>
<variable initial_value="2e-3" name="tau_on" public_interface="out" units="second"/>
<variable initial_value="2e-3" name="tau_off" public_interface="out" units="second"/>
<variable initial_value="60e3" name="G_max_rel" public_interface="out" units="mM_per_sec"/>
<variable initial_value="0.18e-3" name="d_Cai_th" public_interface="out" units="mM"/>
<variable initial_value="0.8e-3" name="Km_rel" public_interface="out" units="mM"/>
<variable initial_value="8.75" name="CSQN_th" public_interface="out" units="mM"/>
<variable initial_value="15" name="CSQN_bar" public_interface="out" units="mM"/>
<variable initial_value="0.8" name="Km_CSQN" public_interface="out" units="mM"/>
<variable initial_value="5.7e-4" name="tau_tr" public_interface="out" units="second"/>
<variable initial_value="0.07" name="TRPN_bar" public_interface="out" units="mM"/>
<variable initial_value="0.05" name="CMDN_bar" public_interface="out" units="mM"/>
<variable initial_value="0.07" name="INDO_bar" public_interface="out" units="mM"/>
<variable initial_value="0.5128e-3" name="Km_TRPN" public_interface="out" units="mM"/>
<variable initial_value="2.38e-3" name="Km_CMDN" public_interface="out" units="mM"/>
<variable initial_value="8.44e-4" name="Km_INDO" public_interface="out" units="mM"/>
</component>
<component name="b1_AR_module">
<variable name="time" public_interface="in" units="second"/>
<variable name="L_totmax" public_interface="in" units="uM"/>
<variable name="sum_b1_AR" public_interface="in" units="uM"/>
<variable name="Gs_tot" public_interface="in" units="uM"/>
<variable name="Kl" public_interface="in" units="uM"/>
<variable name="Kr" public_interface="in" units="uM"/>
<variable name="Kc" public_interface="in" units="uM"/>
<variable name="k_bar_kp" public_interface="in" units="per_sec"/>
<variable name="k_bar_km" public_interface="in" units="per_sec"/>
<variable name="k_p_kap" public_interface="in" units="per_uM_per_sec"/>
<variable name="k_p_kam" public_interface="in" units="per_sec"/>
<variable name="k_g_act" public_interface="in" units="per_sec"/>
<variable name="k_hyd" public_interface="in" units="per_sec"/>
<variable name="k_reassoc" public_interface="in" units="per_uM_per_sec"/>
<variable cmeta:id="LR" name="LR" public_interface="out" units="uM"/>
<variable cmeta:id="LRG" name="LRG" public_interface="out" units="uM"/>
<variable cmeta:id="RG" name="RG" public_interface="out" units="uM"/>
<variable cmeta:id="BARK_DESENS" name="BARK_DESENS" units="uM_per_sec"/>
<variable name="BARK_RESENS" units="uM_per_sec"/>
<variable cmeta:id="PKA_DESENS" name="PKA_DESENS" units="uM_per_sec"/>
<variable name="PKA_RESENS" units="uM_per_sec"/>
<variable cmeta:id="G_ACT" name="G_ACT" units="uM_per_sec"/>
<variable name="HYD" units="uM_per_sec"/>
<variable name="REASSOC" units="uM_per_sec"/>
<variable cmeta:id="L" name="L" public_interface="out" units="uM"/>
<variable cmeta:id="R" name="R" public_interface="out" units="uM"/>
<variable cmeta:id="Gs" name="Gs" public_interface="out" units="uM"/>
<variable initial_value="0.01205" name="b1_AR_tot" public_interface="out" units="uM"/>
<variable initial_value="0" name="b1_AR_d" public_interface="out" units="uM"/>
<variable initial_value="1.154e-3" name="b1_AR_p" public_interface="out" units="uM"/>
<variable initial_value="0.02505" name="Gs_agtp_tot" public_interface="out" units="uM"/>
<variable initial_value="6.446e-4" name="Gs_agdp" public_interface="out" units="uM"/>
<variable initial_value="0.02569" name="Gs_bg" public_interface="out" units="uM"/>
<variable name="PKAC_I" public_interface="in" units="uM"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>LR</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>L</ci>
<ci>R</ci>
</apply>
<ci>Kl</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>LRG</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>LR</ci>
<ci>Gs</ci>
</apply>
<ci>Kr</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>RG</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>R</ci>
<ci>Gs</ci>
</apply>
<ci>Kc</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>BARK_DESENS</ci>
<apply>
<times/>
<ci>k_bar_kp</ci>
<apply>
<plus/>
<ci>LR</ci>
<ci>LRG</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>BARK_RESENS</ci>
<apply>
<times/>
<ci>k_bar_km</ci>
<ci>b1_AR_d</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>PKA_DESENS</ci>
<apply>
<times/>
<ci>k_p_kap</ci>
<ci>PKAC_I</ci>
<ci>b1_AR_tot</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>PKA_RESENS</ci>
<apply>
<times/>
<ci>k_p_kam</ci>
<ci>b1_AR_p</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>G_ACT</ci>
<apply>
<times/>
<ci>k_g_act</ci>
<apply>
<plus/>
<ci>RG</ci>
<ci>LRG</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>HYD</ci>
<apply>
<times/>
<ci>k_hyd</ci>
<ci>Gs_agtp_tot</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>REASSOC</ci>
<apply>
<times/>
<ci>k_reassoc</ci>
<ci>Gs_agdp</ci>
<ci>Gs_bg</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>L</ci>
<apply>
<minus/>
<apply>
<minus/>
<ci>L_totmax</ci>
<ci>LR</ci>
</apply>
<ci>LRG</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>R</ci>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<minus/>
<ci>b1_AR_tot</ci>
<ci>LR</ci>
</apply>
<ci>LRG</ci>
</apply>
<ci>RG</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>Gs</ci>
<apply>
<minus/>
<apply>
<minus/>
<ci>Gs_tot</ci>
<ci>LRG</ci>
</apply>
<ci>RG</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>b1_AR_tot</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<ci>BARK_RESENS</ci>
<ci>BARK_DESENS</ci>
</apply>
<ci>PKA_RESENS</ci>
</apply>
<ci>PKA_DESENS</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>b1_AR_d</ci>
</apply>
<apply>
<minus/>
<ci>BARK_DESENS</ci>
<ci>BARK_RESENS</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>b1_AR_p</ci>
</apply>
<apply>
<minus/>
<ci>PKA_DESENS</ci>
<ci>PKA_RESENS</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Gs_agtp_tot</ci>
</apply>
<apply>
<minus/>
<ci>G_ACT</ci>
<ci>HYD</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Gs_agdp</ci>
</apply>
<apply>
<minus/>
<ci>HYD</ci>
<ci>REASSOC</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Gs_bg</ci>
</apply>
<apply>
<minus/>
<ci>G_ACT</ci>
<ci>REASSOC</ci>
</apply>
</apply>
</math>
</component>
<component name="cAMP_module">
<variable name="time" public_interface="in" units="second"/>
<variable name="AC_tot" public_interface="in" units="uM"/>
<variable name="ATP" public_interface="in" units="uM"/>
<variable name="PDE_tot" public_interface="in" units="uM"/>
<variable name="IBMX_tot" public_interface="in" units="uM"/>
<variable name="Fsk_tot" public_interface="in" units="uM"/>
<variable name="k_ac_basal" public_interface="in" units="per_sec"/>
<variable name="k_ac_gsa" public_interface="in" units="per_sec"/>
<variable name="k_ac_fsk" public_interface="in" units="per_sec"/>
<variable name="k_pde" public_interface="in" units="per_sec"/>
<variable name="Km_basal" public_interface="in" units="uM"/>
<variable name="Km_gsa" public_interface="in" units="uM"/>
<variable name="Km_fsk" public_interface="in" units="uM"/>
<variable name="Km_pde" public_interface="in" units="uM"/>
<variable name="K_gsa" public_interface="in" units="uM"/>
<variable name="K_fsk" public_interface="in" units="uM"/>
<variable name="Ki_ibmx" public_interface="in" units="uM"/>
<variable name="cAMP" public_interface="in" units="uM"/>
<variable cmeta:id="Gsa_GTP" name="Gsa_GTP" units="uM"/>
<variable cmeta:id="FSK" name="Fsk" units="uM"/>
<variable cmeta:id="AC" name="AC" units="uM"/>
<variable cmeta:id="PDE" name="PDE" units="uM"/>
<variable cmeta:id="IBMX" name="IBMX" units="uM"/>
<variable initial_value="0.8453" name="cAMP_tot" public_interface="out" units="uM"/>
<variable cmeta:id="Gsa_GTP_AC" name="Gsa_GTP_AC" units="uM"/>
<variable cmeta:id="Fsk_AC" name="Fsk_AC" units="uM"/>
<variable cmeta:id="AC_ACT_GSA" name="AC_ACT_GSA" units="uM_per_sec"/>
<variable cmeta:id="AC_ACT_BASAL" name="AC_ACT_BASAL" units="uM_per_sec"/>
<variable cmeta:id="AC_ACT_FSK" name="AC_ACT_FSK" units="uM_per_sec"/>
<variable cmeta:id="PDE_ACT" name="PDE_ACT" units="uM_per_sec"/>
<variable name="PDE_IBMX" units="uM"/>
<variable name="Gs_agtp_tot" public_interface="in" units="uM"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>Gsa_GTP_AC</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>Gsa_GTP</ci>
<ci>AC</ci>
</apply>
<ci>K_gsa</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>Fsk_AC</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>Fsk</ci>
<ci>AC</ci>
</apply>
<ci>K_fsk</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>AC_ACT_BASAL</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>k_ac_basal</ci>
<ci>AC</ci>
<ci>ATP</ci>
</apply>
<apply>
<plus/>
<ci>Km_basal</ci>
<ci>ATP</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>AC_ACT_GSA</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>k_ac_gsa</ci>
<ci>Gsa_GTP_AC</ci>
<ci>ATP</ci>
</apply>
<apply>
<plus/>
<ci>Km_gsa</ci>
<ci>ATP</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>AC_ACT_FSK</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>k_ac_fsk</ci>
<ci>Fsk_AC</ci>
<ci>ATP</ci>
</apply>
<apply>
<plus/>
<ci>Km_fsk</ci>
<ci>ATP</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>PDE_ACT</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>k_pde</ci>
<ci>PDE</ci>
<ci>cAMP</ci>
</apply>
<apply>
<plus/>
<ci>Km_pde</ci>
<ci>cAMP</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>PDE_IBMX</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>PDE</ci>
<ci>IBMX</ci>
</apply>
<ci>Ki_ibmx</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>Gsa_GTP</ci>
<apply>
<minus/>
<ci>Gs_agtp_tot</ci>
<ci>Gsa_GTP_AC</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>Fsk</ci>
<apply>
<minus/>
<ci>Fsk_tot</ci>
<ci>Fsk_AC</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>AC</ci>
<apply>
<minus/>
<ci>AC_tot</ci>
<ci>Gsa_GTP_AC</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>PDE</ci>
<apply>
<minus/>
<ci>PDE_tot</ci>
<ci>PDE_IBMX</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>IBMX</ci>
<apply>
<minus/>
<ci>IBMX_tot</ci>
<ci>PDE_IBMX</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>cAMP_tot</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>AC_ACT_BASAL</ci>
<ci>AC_ACT_GSA</ci>
<ci>AC_ACT_FSK</ci>
</apply>
<ci>PDE_ACT</ci>
</apply>
</apply>
</math>
</component>
<component name="PKA_module">
<variable name="PKAI_tot" public_interface="in" units="uM"/>
<variable name="PKAII_tot" public_interface="in" units="uM"/>
<variable name="PKI_tot" public_interface="in" units="uM"/>
<variable name="K_a" public_interface="in" units="uM"/>
<variable name="K_b" public_interface="in" units="uM"/>
<variable name="K_d" public_interface="in" units="uM"/>
<variable name="Ki_pki" public_interface="in" units="uM"/>
<variable cmeta:id="PKI" name="PKI" units="uM"/>
<variable cmeta:id="A2RC_I" name="A2RC_I" units="uM"/>
<variable cmeta:id="A2R_I" name="A2R_I" units="uM"/>
<variable cmeta:id="A2RC_II" name="A2RC_II" units="uM"/>
<variable cmeta:id="A2R_II" name="A2R_II" units="uM"/>
<variable cmeta:id="ARC_I" name="ARC_I" units="uM"/>
<variable cmeta:id="ARC_II" name="ARC_II" units="uM"/>
<variable cmeta:id="PKA_temp" name="PKA_temp" units="uM"/>
<variable cmeta:id="cAMP" name="cAMP" public_interface="out" units="uM"/>
<variable cmeta:id="PKAC_I" name="PKAC_I" public_interface="out" units="uM"/>
<variable cmeta:id="PKAC_II" name="PKAC_II" public_interface="out" units="uM"/>
<variable name="cAMP_tot" public_interface="in" units="uM"/>
<variable initial_value="0" name="zed" units="dimensionless"/>
<variable initial_value="0" name="zed1" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>PKI</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>PKI_tot</ci>
<ci>Ki_pki</ci>
</apply>
<apply>
<plus/>
<ci>Ki_pki</ci>
<ci>PKAC_I</ci>
<ci>PKAC_II</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>A2RC_I</ci>
<apply>
<times/>
<apply>
<divide/>
<ci>PKAC_I</ci>
<ci>K_d</ci>
</apply>
<ci>PKAC_I</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>PKI</ci>
<ci>Ki_pki</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>A2R_I</ci>
<apply>
<times/>
<ci>PKAC_I</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>PKI</ci>
<ci>Ki_pki</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>A2RC_II</ci>
<apply>
<times/>
<apply>
<divide/>
<ci>PKAC_II</ci>
<ci>K_d</ci>
</apply>
<ci>PKAC_II</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>PKI</ci>
<ci>Ki_pki</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>A2R_II</ci>
<apply>
<times/>
<ci>PKAC_II</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>PKI</ci>
<ci>Ki_pki</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>ARC_I</ci>
<apply>
<times/>
<apply>
<divide/>
<ci>K_a</ci>
<ci>cAMP</ci>
</apply>
<ci>A2RC_I</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>ARC_II</ci>
<apply>
<times/>
<apply>
<divide/>
<ci>K_a</ci>
<ci>cAMP</ci>
</apply>
<ci>A2RC_II</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>PKA_temp</ci>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<ci>K_a</ci>
<ci>K_b</ci>
</apply>
<ci>K_d</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>K_a</ci>
<ci>cAMP</ci>
</apply>
<ci>K_d</ci>
</apply>
<apply>
<divide/>
<apply>
<power/>
<ci>cAMP</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>K_d</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>cAMP</ci>
<apply>
<minus/>
<apply>
<minus/>
<ci>cAMP_tot</ci>
<apply>
<plus/>
<ci>ARC_I</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>A2RC_I</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>A2R_I</ci>
</apply>
</apply>
</apply>
<apply>
<plus/>
<ci>ARC_II</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>A2RC_II</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>A2R_II</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>zed</ci>
<apply>
<minus/>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>PKAI_tot</ci>
<apply>
<power/>
<ci>cAMP</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<times/>
<ci>PKAC_I</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>PKI</ci>
<ci>Ki_pki</ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>PKA_temp</ci>
<ci>PKAC_I</ci>
</apply>
<apply>
<power/>
<ci>cAMP</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>zed1</ci>
<apply>
<minus/>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>PKAII_tot</ci>
<apply>
<power/>
<ci>cAMP</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<times/>
<ci>PKAC_II</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>PKI</ci>
<ci>Ki_pki</ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>PKA_temp</ci>
<ci>PKAC_II</ci>
</apply>
<apply>
<power/>
<ci>cAMP</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="PLB_module">
<variable name="time" public_interface="in" units="second"/>
<variable name="PLB_tot" public_interface="in" units="uM"/>
<variable name="PP1_tot" public_interface="in" units="uM"/>
<variable name="Inhib1_tot" public_interface="in" units="uM"/>
<variable name="k_pka_plb" public_interface="in" units="per_sec"/>
<variable name="Km_pka_plb" public_interface="in" units="uM"/>
<variable name="k_pp1_plb" public_interface="in" units="per_sec"/>
<variable name="Km_pp1_plb" public_interface="in" units="uM"/>
<variable name="k_pka_i1" public_interface="in" units="per_sec"/>
<variable name="Km_pka_i1" public_interface="in" units="uM"/>
<variable name="Vmax_pp2a_i1" public_interface="in" units="uM_per_sec"/>
<variable name="Km_pp2a_i1" public_interface="in" units="uM"/>
<variable name="Ki_inhib1" public_interface="in" units="uM"/>
<variable name="PLB" units="uM"/>
<variable cmeta:id="PLB_PHOSPH" name="PLB_PHOSPH" units="uM_per_sec"/>
<variable cmeta:id="PLB_DEPHOSPH" name="PLB_DEPHOSPH" units="uM_per_sec"/>
<variable name="Inhib1" units="uM"/>
<variable cmeta:id="Inhib1p_PP1" name="Inhib1p_PP1" units="uM"/>
<variable cmeta:id="Inhib1_PHOSPH" name="Inhib1_PHOSPH" units="uM_per_sec"/>
<variable name="Inhib1_DEPHOSPH" units="uM_per_sec"/>
<variable initial_value="4.105" name="PLB_p" units="uM"/>
<variable initial_value="0.0526" name="Inhib1p_tot" units="uM"/>
<variable cmeta:id="Inhib1p" name="Inhib1p" units="uM"/>
<variable cmeta:id="PP1" name="PP1" units="uM"/>
<variable name="frac_PLB_p" units="dimensionless"/>
<variable name="frac_PLB" public_interface="out" units="dimensionless"/>
<variable name="frac_PLB_o" public_interface="out" units="dimensionless"/>
<variable name="PKAC_I" public_interface="in" units="uM"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>PLB</ci>
<apply>
<minus/>
<ci>PLB_tot</ci>
<ci>PLB_p</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>PLB_PHOSPH</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>k_pka_plb</ci>
<ci>PKAC_I</ci>
<ci>PLB</ci>
</apply>
<apply>
<plus/>
<ci>Km_pka_plb</ci>
<ci>PLB</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>PLB_DEPHOSPH</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>k_pp1_plb</ci>
<ci>PP1</ci>
<ci>PLB_p</ci>
</apply>
<apply>
<plus/>
<ci>Km_pp1_plb</ci>
<ci>PLB_p</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>Inhib1</ci>
<apply>
<minus/>
<ci>Inhib1_tot</ci>
<ci>Inhib1p_tot</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>Inhib1p_PP1</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>Inhib1p</ci>
<ci>PP1</ci>
</apply>
<ci>Ki_inhib1</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>Inhib1_PHOSPH</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>k_pka_i1</ci>
<ci>PKAC_I</ci>
<ci>Inhib1</ci>
</apply>
<apply>
<plus/>
<ci>Km_pka_i1</ci>
<ci>Inhib1</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>Inhib1_DEPHOSPH</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>Vmax_pp2a_i1</ci>
<ci>Inhib1p_tot</ci>
</apply>
<apply>
<plus/>
<ci>Km_pp2a_i1</ci>
<ci>Inhib1p_tot</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>PLB_p</ci>
</apply>
<apply>
<minus/>
<ci>PLB_PHOSPH</ci>
<ci>PLB_DEPHOSPH</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Inhib1p_tot</ci>
</apply>
<apply>
<minus/>
<ci>Inhib1_PHOSPH</ci>
<ci>Inhib1_DEPHOSPH</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>Inhib1p</ci>
<apply>
<minus/>
<ci>Inhib1p_tot</ci>
<ci>Inhib1p_PP1</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>PP1</ci>
<apply>
<minus/>
<ci>PP1_tot</ci>
<ci>Inhib1p_PP1</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>frac_PLB_p</ci>
<apply>
<divide/>
<ci>PLB_p</ci>
<ci>PLB_tot</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>frac_PLB</ci>
<apply>
<divide/>
<ci>PLB</ci>
<ci>PLB_tot</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>frac_PLB_o</ci>
<cn cellml:units="dimensionless">0.9613</cn>
</apply>
</math>
</component>
<component name="LCC_module">
<variable name="time" public_interface="in" units="second"/>
<variable name="epsilon" public_interface="in" units="dimensionless"/>
<variable name="LCC_tot" public_interface="in" units="uM"/>
<variable name="PP1_lcc_tot" public_interface="in" units="uM"/>
<variable name="PP2A_lcc_tot" public_interface="in" units="uM"/>
<variable name="k_pka_lcc" public_interface="in" units="per_sec"/>
<variable name="Km_pka_lcc" public_interface="in" units="uM"/>
<variable name="k_pp1_lcc" public_interface="in" units="per_sec"/>
<variable name="Km_pp1_lcc" public_interface="in" units="uM"/>
<variable name="k_pp2a_lcc" public_interface="in" units="per_sec"/>
<variable name="Km_pp2a_lcc" public_interface="in" units="uM"/>
<variable name="LCCa" units="uM"/>
<variable cmeta:id="LCCa_PHOSPH" name="LCCa_PHOSPH" units="uM_per_sec"/>
<variable name="LCCa_DEPHOSPH" units="uM_per_sec"/>
<variable name="LCCb" units="uM"/>
<variable cmeta:id="LCCb_PHOSPH" name="LCCb_PHOSPH" units="uM_per_sec"/>
<variable name="LCCb_DEPHOSPH" units="uM_per_sec"/>
<variable initial_value="5.103e-3" name="LCCa_p" units="uM"/>
<variable initial_value="5.841e-3" name="LCCb_p" units="uM"/>
<variable name="frac_LCCa_p" public_interface="out" units="dimensionless"/>
<variable name="frac_LCCa_po" public_interface="out" units="dimensionless"/>
<variable name="frac_LCCb_p" public_interface="out" units="dimensionless"/>
<variable name="frac_LCCb_po" public_interface="out" units="dimensionless"/>
<variable name="PKAC_II" public_interface="in" units="uM"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>LCCa</ci>
<apply>
<minus/>
<ci>LCC_tot</ci>
<ci>LCCa_p</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>LCCa_PHOSPH</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>epsilon</ci>
<ci>k_pka_lcc</ci>
<ci>PKAC_II</ci>
<ci>LCCa</ci>
</apply>
<apply>
<plus/>
<ci>Km_pka_lcc</ci>
<apply>
<times/>
<ci>epsilon</ci>
<ci>LCCa</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>LCCa_DEPHOSPH</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>epsilon</ci>
<ci>k_pp2a_lcc</ci>
<ci>PP2A_lcc_tot</ci>
<ci>LCCa_p</ci>
</apply>
<apply>
<plus/>
<ci>Km_pp2a_lcc</ci>
<apply>
<times/>
<ci>epsilon</ci>
<ci>LCCa_p</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>LCCb</ci>
<apply>
<minus/>
<ci>LCC_tot</ci>
<ci>LCCb_p</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>LCCb_PHOSPH</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>epsilon</ci>
<ci>k_pka_lcc</ci>
<ci>PKAC_II</ci>
<ci>LCCb</ci>
</apply>
<apply>
<plus/>
<ci>Km_pka_lcc</ci>
<apply>
<times/>
<ci>epsilon</ci>
<ci>LCCb</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>LCCb_DEPHOSPH</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>epsilon</ci>
<ci>k_pp1_lcc</ci>
<ci>PP1_lcc_tot</ci>
<ci>LCCb_p</ci>
</apply>
<apply>
<plus/>
<ci>Km_pp1_lcc</ci>
<apply>
<times/>
<ci>epsilon</ci>
<ci>LCCb_p</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>LCCa_p</ci>
</apply>
<apply>
<minus/>
<ci>LCCa_PHOSPH</ci>
<ci>LCCa_DEPHOSPH</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>LCCb_p</ci>
</apply>
<apply>
<minus/>
<ci>LCCb_PHOSPH</ci>
<ci>LCCb_DEPHOSPH</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>frac_LCCa_p</ci>
<apply>
<divide/>
<ci>LCCa_p</ci>
<ci>LCC_tot</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>frac_LCCa_po</ci>
<cn cellml:units="dimensionless">0.2041</cn>
</apply>
<apply>
<eq/>
<ci>frac_LCCb_p</ci>
<apply>
<divide/>
<ci>LCCb_p</ci>
<ci>LCC_tot</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>frac_LCCb_po</ci>
<cn cellml:units="dimensionless">0.2336</cn>
</apply>
</math>
</component>
<component name="Nernst_Potentials">
<variable name="E_Na" public_interface="out" units="mV"/>
<variable name="E_K" public_interface="out" units="mV"/>
<variable name="E_Ca" public_interface="out" units="mV"/>
<variable name="E_Cl" public_interface="out" units="mV"/>
<variable initial_value="8314" name="R" units="joules_per_kmole_kelvin"/>
<variable initial_value="96485" name="Frdy" public_interface="out" units="coulombs_per_mole"/>
<variable name="FoRT" public_interface="out" units="per_mV"/>
<variable initial_value="1" name="z_Na" public_interface="out" units="dimensionless"/>
<variable initial_value="1" name="z_K" public_interface="out" units="dimensionless"/>
<variable initial_value="2" name="z_Ca" public_interface="out" units="dimensionless"/>
<variable name="Temp" public_interface="in" units="kelvin"/>
<variable name="Na_ext" public_interface="in" units="mM"/>
<variable name="K_ext" public_interface="in" units="mM"/>
<variable name="Ca_ext" public_interface="in" units="mM"/>
<variable name="Na_i" public_interface="in" units="mM"/>
<variable name="K_i" public_interface="in" units="mM"/>
<variable name="Ca_i" public_interface="in" units="mM"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>FoRT</ci>
<apply>
<divide/>
<apply>
<divide/>
<ci>Frdy</ci>
<ci>R</ci>
</apply>
<ci>Temp</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>E_Na</ci>
<apply>
<times/>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<times/>
<ci>FoRT</ci>
<ci>z_Na</ci>
</apply>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<ci>Na_ext</ci>
<ci>Na_i</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>E_K</ci>
<apply>
<times/>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<times/>
<ci>FoRT</ci>
<ci>z_K</ci>
</apply>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<ci>K_ext</ci>
<ci>K_i</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>E_Ca</ci>
<apply>
<times/>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<times/>
<ci>FoRT</ci>
<ci>z_Ca</ci>
</apply>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<ci>Ca_ext</ci>
<ci>Ca_i</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>E_Cl</ci>
<apply>
<minus/>
<cn cellml:units="mV">40</cn>
</apply>
</apply>
</math>
</component>
<component name="Fast_Na_Current">
<variable name="time" public_interface="in" units="second"/>
<variable name="am" units="per_sec"/>
<variable name="bm" units="per_sec"/>
<variable name="ah" units="per_sec"/>
<variable name="aj" units="per_sec"/>
<variable name="bh" units="per_sec"/>
<variable name="bj" units="per_sec"/>
<variable initial_value="1.4e-3" name="m" units="dimensionless"/>
<variable initial_value="0.99" name="h" units="dimensionless"/>
<variable initial_value="0.99" name="j" units="dimensionless"/>
<variable name="I_Na" public_interface="out" units="uA_per_uF"/>
<variable name="V_m" public_interface="in" units="mV"/>
<variable name="E_Na" public_interface="in" units="mV"/>
<variable name="G_Na" public_interface="in" units="mS_per_uF"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>am</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_mV_per_second">0.32</cn>
<apply>
<plus/>
<ci>V_m</ci>
<cn cellml:units="mV">47.13</cn>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_mV">0.1</cn>
</apply>
<apply>
<plus/>
<ci>V_m</ci>
<cn cellml:units="mV">47.13</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>bm</ci>
<apply>
<times/>
<cn cellml:units="per_sec">0.08</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>V_m</ci>
</apply>
<cn cellml:units="mV">11</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>ah</ci>
<piecewise>
<piece>
<cn cellml:units="per_sec">0</cn>
<apply>
<geq/>
<ci>V_m</ci>
<apply>
<minus/>
<cn cellml:units="mV">40</cn>
</apply>
</apply>
</piece>
<otherwise>
<apply>
<times/>
<cn cellml:units="per_sec">0.135</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<cn cellml:units="mV">80</cn>
<ci>V_m</ci>
</apply>
<apply>
<minus/>
<cn cellml:units="mV">6.8</cn>
</apply>
</apply>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>aj</ci>
<piecewise>
<piece>
<cn cellml:units="per_sec">0</cn>
<apply>
<geq/>
<ci>V_m</ci>
<apply>
<minus/>
<cn cellml:units="mV">40</cn>
</apply>
</apply>
</piece>
<otherwise>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_mV_per_second" type="e-notation">1.2714<sep/>5</cn>
</apply>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="per_mV">0.2444</cn>
<ci>V_m</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="per_sec" type="e-notation">3.474<sep/>-5</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_mV">0.04391</cn>
</apply>
<ci>V_m</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<ci>V_m</ci>
<cn cellml:units="mV">37.78</cn>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="per_mV">0.311</cn>
<apply>
<plus/>
<ci>V_m</ci>
<cn cellml:units="mV">79.23</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>bh</ci>
<piecewise>
<piece>
<apply>
<divide/>
<cn cellml:units="per_sec">1</cn>
<apply>
<times/>
<cn cellml:units="dimensionless">0.13</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<plus/>
<ci>V_m</ci>
<cn cellml:units="mV">10.66</cn>
</apply>
</apply>
<cn cellml:units="mV">11.1</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<geq/>
<ci>V_m</ci>
<apply>
<minus/>
<cn cellml:units="mV">40</cn>
</apply>
</apply>
</piece>
<otherwise>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="per_sec">3.56</cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="per_mV">0.079</cn>
<ci>V_m</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="per_sec" type="e-notation">3.1<sep/>5</cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="per_mV">0.35</cn>
<ci>V_m</ci>
</apply>
</apply>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>bj</ci>
<piecewise>
<piece>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_sec">0.3</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_mV" type="e-notation">2.575<sep/>-7</cn>
</apply>
<ci>V_m</ci>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_mV">0.1</cn>
</apply>
<apply>
<plus/>
<ci>V_m</ci>
<cn cellml:units="mV">32</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<geq/>
<ci>V_m</ci>
<apply>
<minus/>
<cn cellml:units="mV">40</cn>
</apply>
</apply>
</piece>
<otherwise>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_sec">0.1212</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_mV">0.01052</cn>
</apply>
<ci>V_m</ci>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_mV">0.1378</cn>
</apply>
<apply>
<plus/>
<ci>V_m</ci>
<cn cellml:units="mV">40.14</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>m</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless" type="e-notation">1<sep/>3</cn>
<apply>
<minus/>
<apply>
<times/>
<ci>am</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>m</ci>
</apply>
</apply>
<apply>
<times/>
<ci>bm</ci>
<ci>m</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>h</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless" type="e-notation">1<sep/>3</cn>
<apply>
<minus/>
<apply>
<times/>
<ci>ah</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>h</ci>
</apply>
</apply>
<apply>
<times/>
<ci>bh</ci>
<ci>h</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>j</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless" type="e-notation">1<sep/>3</cn>
<apply>
<minus/>
<apply>
<times/>
<ci>aj</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>j</ci>
</apply>
</apply>
<apply>
<times/>
<ci>bj</ci>
<ci>j</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>I_Na</ci>
<apply>
<times/>
<ci>G_Na</ci>
<apply>
<power/>
<ci>m</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>h</ci>
<ci>j</ci>
<apply>
<minus/>
<ci>V_m</ci>
<ci>E_Na</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="L_Type_Calcium_Current">
<variable name="a_lcc" units="per_sec"/>
<variable name="b_lcc" units="per_sec"/>
<variable name="f_lcc" units="per_sec"/>
<variable name="y_lcc_inf" units="dimensionless"/>
<variable name="tau_y_lcc" units="second"/>
<variable name="gamma" units="per_sec"/>
<variable name="v_gamma" units="per_sec"/>
<variable name="v_omega" units="per_sec"/>
<variable initial_value="0" name="v" units="dimensionless"/>
<variable initial_value="0" name="w" units="dimensionless"/>
<variable initial_value="0.13" name="x" units="dimensionless"/>
<variable initial_value="0.96" name="y" units="dimensionless"/>
<variable initial_value="0.92" name="z" units="dimensionless"/>
<variable name="i_bar_Ca" units="uA_per_uF"/>
<variable name="i_bar_K" units="uA_per_uF"/>
<variable name="f_avail" units="dimensionless"/>
<variable name="I_Ca" public_interface="out" units="uA_per_uF"/>
<variable name="I_CaK" public_interface="out" units="uA_per_uF"/>
<variable name="I_Ca_tot" public_interface="out" units="uA_per_uF"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="K_ext" public_interface="in" units="mM"/>
<variable name="Ca_ext" public_interface="in" units="mM"/>
<variable name="f" public_interface="in" units="per_sec"/>
<variable name="g" public_interface="in" units="per_sec"/>
<variable name="gamma_o" public_interface="in" units="per_mM_per_sec"/>
<variable name="omega" public_interface="in" units="per_sec"/>
<variable name="p_Ca" public_interface="in" units="cm_per_sec"/>
<variable name="p_K" public_interface="in" units="cm_per_sec"/>
<variable name="N_lcc" public_interface="in" units="dimensionless"/>
<variable name="I_Ca05" public_interface="in" units="uA_per_uF"/>
<variable name="frac_LCCa_p" public_interface="in" units="dimensionless"/>
<variable name="frac_LCCa_po" public_interface="in" units="dimensionless"/>
<variable name="frac_LCCb_p" public_interface="in" units="dimensionless"/>
<variable name="frac_LCCb_po" public_interface="in" units="dimensionless"/>
<variable name="Frdy" public_interface="in" units="coulombs_per_mole"/>
<variable name="FoRT" public_interface="in" units="per_mV"/>
<variable name="K_i" public_interface="in" units="mM"/>
<variable name="Ca_i" public_interface="in" units="mM"/>
<variable name="V_m" public_interface="in" units="mV"/>
<variable initial_value="10e5" name="alpha" units="ibar_to_I"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>a_lcc</ci>
<apply>
<times/>
<cn cellml:units="per_sec">400</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V_m</ci>
<cn cellml:units="mV">2</cn>
</apply>
<cn cellml:units="mV">10</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>b_lcc</ci>
<apply>
<times/>
<cn cellml:units="per_sec">50</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<plus/>
<ci>V_m</ci>
<cn cellml:units="mV">2</cn>
</apply>
</apply>
<cn cellml:units="mV">13</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>f_lcc</ci>
<apply>
<times/>
<ci>f</ci>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">0.375</cn>
<ci>frac_LCCa_p</ci>
</apply>
<ci>frac_LCCa_po</ci>
</apply>
<cn cellml:units="dimensionless">0.625</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>y_lcc_inf</ci>
<apply>
<plus/>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V_m</ci>
<cn cellml:units="mV">55</cn>
</apply>
<cn cellml:units="mV">7.5</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<divide/>
<cn cellml:units="dimensionless">0.1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<apply>
<minus/>
<ci>V_m</ci>
</apply>
<cn cellml:units="mV">21</cn>
</apply>
<cn cellml:units="mV">6</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_y_lcc</ci>
<apply>
<plus/>
<cn cellml:units="second">0.02</cn>
<apply>
<divide/>
<cn cellml:units="second">0.3</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V_m</ci>
<cn cellml:units="mV">30</cn>
</apply>
<cn cellml:units="mV">9.5</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>gamma</ci>
<apply>
<times/>
<ci>gamma_o</ci>
<ci>Ca_i</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>v_gamma</ci>
<apply>
<times/>
<ci>gamma</ci>
<apply>
<plus/>
<apply>
<power/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>v</ci>
</apply>
<cn cellml:units="dimensionless">4</cn>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>v</ci>
<apply>
<power/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>v</ci>
</apply>
<cn cellml:units="dimensionless">3</cn>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">4</cn>
<apply>
<power/>
<ci>v</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<apply>
<power/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>v</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">8</cn>
<apply>
<power/>
<ci>v</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>v</ci>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">16</cn>
<apply>
<power/>
<ci>v</ci>
<cn cellml:units="dimensionless">4</cn>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>f_lcc</ci>
<ci>g</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>v_omega</ci>
<apply>
<times/>
<ci>omega</ci>
<apply>
<plus/>
<apply>
<power/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>w</ci>
</apply>
<cn cellml:units="dimensionless">4</cn>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">0.5</cn>
<ci>w</ci>
<apply>
<power/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>w</ci>
</apply>
<cn cellml:units="dimensionless">3</cn>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">0.25</cn>
<apply>
<power/>
<ci>w</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<apply>
<power/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>w</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">0.125</cn>
<apply>
<power/>
<ci>w</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>w</ci>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">0.0625</cn>
<apply>
<power/>
<ci>w</ci>
<cn cellml:units="dimensionless">4</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>v</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>a_lcc</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>v</ci>
</apply>
</apply>
<apply>
<times/>
<ci>b_lcc</ci>
<ci>v</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>w</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>a_lcc</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>w</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<divide/>
<ci>b_lcc</ci>
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<variable name="s_toss" units="dimensionless"/>
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<eq/>
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<divide/>
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<minus/>
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<cn cellml:units="mV">6.8841</cn>
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<eq/>
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<times/>
<cn cellml:units="dimensionless">98.9</cn>
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<exp/>
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<times/>
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<minus/>
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<power/>
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<divide/>
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<minus/>
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<diff/>
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<ci>s_toss</ci>
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<eq/>
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<ci>G_to</ci>
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<plus/>
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<ci>V_m</ci>
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<variable name="tau_r_ss" units="second"/>
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<minus/>
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<exp/>
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<times/>
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<exp/>
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<times/>
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<minus/>
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<plus/>
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<plus/>
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<eq/>
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<minus/>
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<ci>E_K</ci>
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</apply>
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<variable name="b_Ki" units="dimensionless"/>
<variable name="Ki_ss" units="dimensionless"/>
<variable name="I_Ki" public_interface="out" units="uA_per_uF"/>
<variable name="V_m" public_interface="in" units="mV"/>
<variable name="E_K" public_interface="in" units="mV"/>
<variable name="G_Ki_bar" public_interface="in" units="mS_per_uF"/>
<variable name="K_ext" public_interface="in" units="mM"/>
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<eq/>
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<divide/>
<cn cellml:units="dimensionless">1.02</cn>
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<plus/>
<cn cellml:units="dimensionless">1</cn>
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<exp/>
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<times/>
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<minus/>
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<minus/>
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<plus/>
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<times/>
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<exp/>
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<minus/>
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<plus/>
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<exp/>
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<times/>
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<minus/>
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<minus/>
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<exp/>
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<times/>
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<minus/>
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<minus/>
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<ci>E_K</ci>
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<variable name="I_Kp" public_interface="out" units="uA_per_uF"/>
<variable name="V_m" public_interface="in" units="mV"/>
<variable name="E_K" public_interface="in" units="mV"/>
<variable name="G_Kp" public_interface="in" units="mS_per_uF"/>
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<divide/>
<cn cellml:units="dimensionless">1</cn>
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<plus/>
<cn cellml:units="dimensionless">1</cn>
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<exp/>
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<divide/>
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<minus/>
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<times/>
<ci>G_Kp</ci>
<ci>Kp</ci>
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<minus/>
<ci>V_m</ci>
<ci>E_K</ci>
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</apply>
</apply>
</math>
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<variable name="s5" units="dimensionless"/>
<variable name="I_NCX" public_interface="out" units="uA_per_uF"/>
<variable name="Na_ext" public_interface="in" units="mM"/>
<variable name="Ca_ext" public_interface="in" units="mM"/>
<variable name="k_NaCa" public_interface="in" units="uA_per_uF"/>
<variable name="Km_Na" public_interface="in" units="mM"/>
<variable name="Km_Ca" public_interface="in" units="mM"/>
<variable name="k_sat" public_interface="in" units="dimensionless"/>
<variable name="eta" public_interface="in" units="dimensionless"/>
<variable name="FoRT" public_interface="in" units="per_mV"/>
<variable name="Na_i" public_interface="in" units="mM"/>
<variable name="Ca_i" public_interface="in" units="mM"/>
<variable name="V_m" public_interface="in" units="mV"/>
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<times/>
<cn cellml:units="per_mM4">1</cn>
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<exp/>
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<times/>
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<times/>
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<times/>
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<minus/>
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<power/>
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<times/>
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<times/>
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<plus/>
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<power/>
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<power/>
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<plus/>
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<plus/>
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<exp/>
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<times/>
<apply>
<minus/>
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<apply>
<minus/>
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<variable name="f_NaK" units="dimensionless"/>
<variable name="I_NaK" public_interface="out" units="uA_per_uF"/>
<variable name="Na_ext" public_interface="in" units="mM"/>
<variable name="K_ext" public_interface="in" units="mM"/>
<variable name="I_bar_NaK" public_interface="in" units="uA_per_uF"/>
<variable name="Km_Nai" public_interface="in" units="mM"/>
<variable name="Km_Ko" public_interface="in" units="mM"/>
<variable name="FoRT" public_interface="in" units="per_mV"/>
<variable name="Na_i" public_interface="in" units="mM"/>
<variable name="V_m" public_interface="in" units="mV"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>sigma</ci>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<ci>Na_ext</ci>
<cn cellml:units="mM">67.3</cn>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
<cn cellml:units="dimensionless">7</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>f_NaK</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<times/>
<cn cellml:units="dimensionless">0.1245</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.1</cn>
</apply>
<ci>V_m</ci>
<ci>FoRT</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">0.0365</cn>
<ci>sigma</ci>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<ci>V_m</ci>
</apply>
<ci>FoRT</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>I_NaK</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>I_bar_NaK</ci>
<ci>f_NaK</ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>Km_Nai</ci>
<ci>Na_i</ci>
</apply>
<cn cellml:units="dimensionless">1.5</cn>
</apply>
</apply>
</apply>
<ci>K_ext</ci>
</apply>
<apply>
<plus/>
<ci>K_ext</ci>
<ci>Km_Ko</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Sarcolemmal_Ca_Pump_Current">
<variable name="I_PCa" public_interface="out" units="uA_per_uF"/>
<variable name="I_bar_PCa" public_interface="in" units="uA_per_uF"/>
<variable name="Km_PCa" public_interface="in" units="mM"/>
<variable name="Ca_i" public_interface="in" units="mM"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>I_PCa</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>I_bar_PCa</ci>
<ci>Ca_i</ci>
</apply>
<apply>
<plus/>
<ci>Km_PCa</ci>
<ci>Ca_i</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Ca_Background_Current">
<variable name="I_CaB" public_interface="out" units="uA_per_uF"/>
<variable name="V_m" public_interface="in" units="mV"/>
<variable name="E_Ca" public_interface="in" units="mV"/>
<variable name="G_CaB" public_interface="in" units="uA_per_uF"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>I_CaB</ci>
<apply>
<times/>
<ci>G_CaB</ci>
<apply>
<minus/>
<ci>V_m</ci>
<ci>E_Ca</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Na_Background_Current">
<variable name="I_NaB" public_interface="out" units="uA_per_uF"/>
<variable name="V_m" public_interface="in" units="mV"/>
<variable name="E_Na" public_interface="in" units="mV"/>
<variable name="G_NaB" public_interface="in" units="uA_per_uF"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>I_NaB</ci>
<apply>
<times/>
<ci>G_NaB</ci>
<apply>
<minus/>
<ci>V_m</ci>
<ci>E_Na</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Total_Membrane_Currents">
<variable name="I_Na_tot" public_interface="out" units="uA_per_uF"/>
<variable name="I_K_tot" public_interface="out" units="uA_per_uF"/>
<variable name="I_Ca_tot" public_interface="out" units="uA_per_uF"/>
<variable name="I_Na" public_interface="in" units="uA_per_uF"/>
<variable name="I_NaB" public_interface="in" units="uA_per_uF"/>
<variable name="I_NCX" public_interface="in" units="uA_per_uF"/>
<variable name="I_NaK" public_interface="in" units="uA_per_uF"/>
<variable name="I_to" public_interface="in" units="uA_per_uF"/>
<variable name="I_ss" public_interface="in" units="uA_per_uF"/>
<variable name="I_Ki" public_interface="in" units="uA_per_uF"/>
<variable name="I_Kp" public_interface="in" units="uA_per_uF"/>
<variable name="I_CaK" public_interface="in" units="uA_per_uF"/>
<variable name="I_Ca" public_interface="in" units="uA_per_uF"/>
<variable name="I_CaB" public_interface="in" units="uA_per_uF"/>
<variable name="I_PCa" public_interface="in" units="uA_per_uF"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>I_Na_tot</ci>
<apply>
<plus/>
<ci>I_Na</ci>
<ci>I_NaB</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">3</cn>
<ci>I_NCX</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">3</cn>
<ci>I_NaK</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>I_K_tot</ci>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<ci>I_to</ci>
<ci>I_ss</ci>
<ci>I_Ki</ci>
<ci>I_Kp</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>I_NaK</ci>
</apply>
</apply>
<ci>I_CaK</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>I_Ca_tot</ci>
<apply>
<minus/>
<apply>
<plus/>
<ci>I_Ca</ci>
<ci>I_CaB</ci>
<ci>I_PCa</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>I_NCX</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Calcium_Induced_Calcium_Release">
<variable name="t_rel_sub" units="second"/>
<variable name="ryr_on" units="dimensionless"/>
<variable name="ryr_off" units="dimensionless"/>
<variable name="g_rel" units="per_sec"/>
<variable name="I_rel" public_interface="out" units="mM_per_sec"/>
<variable name="tau_on" public_interface="in" units="second"/>
<variable name="tau_off" public_interface="in" units="second"/>
<variable name="G_max_rel" public_interface="in" units="mM_per_sec"/>
<variable name="I_Ca_tot" public_interface="in" units="uA_per_uF"/>
<variable name="Ca_jsr" public_interface="in" units="mM"/>
<variable name="Ca_i" public_interface="in" units="mM"/>
<variable name="trel" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>t_rel_sub</ci>
<apply>
<plus/>
<ci>trel</ci>
<cn cellml:units="second" type="e-notation">2<sep/>-3</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>ryr_on</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>t_rel_sub</ci>
</apply>
<ci>tau_on</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>ryr_off</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>t_rel_sub</ci>
</apply>
<ci>tau_off</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>g_rel</ci>
<apply>
<divide/>
<ci>G_max_rel</ci>
<apply>
<times/>
<cn cellml:units="mM">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>I_Ca_tot</ci>
<cn cellml:units="uA_per_uF">5</cn>
</apply>
<cn cellml:units="uA_per_uF">0.9</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>I_rel</ci>
<apply>
<times/>
<ci>g_rel</ci>
<ci>ryr_on</ci>
<ci>ryr_off</ci>
<apply>
<minus/>
<ci>Ca_jsr</ci>
<ci>Ca_i</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Other_SR_Fluxes_and_Concentrations">
<variable name="Km_up" units="mM"/>
<variable name="I_up" public_interface="out" units="mM_per_sec"/>
<variable name="I_leak" public_interface="out" units="mM_per_sec"/>
<variable name="I_tr" units="mM_per_sec"/>
<variable name="B_jsr" units="dimensionless"/>
<variable initial_value="1.92" name="Ca_nsr" public_interface="out" units="mM"/>
<variable initial_value="1.92" name="Ca_jsr" public_interface="out" units="mM"/>
<variable name="SR_content" units="uM"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="V_myo" public_interface="in" units="uL"/>
<variable name="V_nsr" public_interface="in" units="uL"/>
<variable name="V_jsr" public_interface="in" units="uL"/>
<variable name="I_up_bar" public_interface="in" units="mM_per_sec"/>
<variable name="Km_up0" public_interface="in" units="mM"/>
<variable name="NSR_bar" public_interface="in" units="mM"/>
<variable name="CSQN_bar" public_interface="in" units="mM"/>
<variable name="Km_CSQN" public_interface="in" units="mM"/>
<variable name="tau_tr" public_interface="in" units="second"/>
<variable name="frac_PLB" public_interface="in" units="dimensionless"/>
<variable name="frac_PLB_o" public_interface="in" units="dimensionless"/>
<variable name="I_rel" public_interface="in" units="mM_per_sec"/>
<variable name="Ca_i" public_interface="in" units="mM"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>Km_up</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>Km_up0</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>frac_PLB</ci>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>frac_PLB_o</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>I_up</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>I_up_bar</ci>
<apply>
<power/>
<ci>Ca_i</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<plus/>
<apply>
<power/>
<ci>Km_up</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<apply>
<power/>
<ci>Ca_i</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>I_leak</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>I_up_bar</ci>
<ci>Ca_nsr</ci>
</apply>
<ci>NSR_bar</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>I_tr</ci>
<apply>
<divide/>
<apply>
<minus/>
<ci>Ca_nsr</ci>
<ci>Ca_jsr</ci>
</apply>
<ci>tau_tr</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>B_jsr</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<ci>CSQN_bar</ci>
<ci>Km_CSQN</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>Km_CSQN</ci>
<ci>Ca_jsr</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_nsr</ci>
</apply>
<apply>
<minus/>
<apply>
<minus/>
<ci>I_up</ci>
<ci>I_leak</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>I_tr</ci>
<ci>V_jsr</ci>
</apply>
<ci>V_nsr</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_jsr</ci>
</apply>
<apply>
<times/>
<ci>B_jsr</ci>
<apply>
<minus/>
<ci>I_tr</ci>
<ci>I_rel</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>SR_content</ci>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<plus/>
<ci>Ca_jsr</ci>
<apply>
<divide/>
<ci>Ca_jsr</ci>
<ci>B_jsr</ci>
</apply>
</apply>
<ci>V_jsr</ci>
</apply>
<ci>V_myo</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>Ca_nsr</ci>
<ci>V_nsr</ci>
</apply>
<ci>V_myo</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Cytoplasmic_Calcium_Buffering">
<variable name="b_trpn" units="dimensionless"/>
<variable name="b_cmdn" units="dimensionless"/>
<variable name="b_indo" units="dimensionless"/>
<variable name="B_myo" public_interface="out" units="dimensionless"/>
<variable name="TRPN_bar" public_interface="in" units="mM"/>
<variable name="CMDN_bar" public_interface="in" units="mM"/>
<variable name="INDO_bar" public_interface="in" units="mM"/>
<variable name="Km_TRPN" public_interface="in" units="mM"/>
<variable name="Km_CMDN" public_interface="in" units="mM"/>
<variable name="Km_INDO" public_interface="in" units="mM"/>
<variable name="Ca_i" public_interface="in" units="mM"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>b_trpn</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>TRPN_bar</ci>
<ci>Km_TRPN</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>Km_TRPN</ci>
<ci>Ca_i</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>b_cmdn</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>CMDN_bar</ci>
<ci>Km_CMDN</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>Km_CMDN</ci>
<ci>Ca_i</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>b_indo</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>INDO_bar</ci>
<ci>Km_INDO</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>Km_INDO</ci>
<ci>Ca_i</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>B_myo</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<ci>b_cmdn</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>b_trpn</ci>
</apply>
<ci>b_indo</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Ion_Concentrations_and_Membrane_Potential">
<variable initial_value="16" name="Na_i" public_interface="out" units="mM"/>
<variable initial_value="145" name="K_i" public_interface="out" units="mM"/>
<variable initial_value="1.58e-4" name="Ca_i" public_interface="out" units="mM"/>
<variable initial_value="-85.66" name="V_m" public_interface="out" units="mV"/>
<variable initial_value="0.9" name="trel" public_interface="out" units="second"/>
<variable name="I_app" units="uA_per_uF"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="V_myo" public_interface="in" units="uL"/>
<variable name="V_nsr" public_interface="in" units="uL"/>
<variable name="V_jsr" public_interface="in" units="uL"/>
<variable name="A_Cap" public_interface="in" units="cm2"/>
<variable name="Frdy" public_interface="in" units="coulombs_per_mole"/>
<variable name="z_Na" public_interface="in" units="dimensionless"/>
<variable name="z_K" public_interface="in" units="dimensionless"/>
<variable name="z_Ca" public_interface="in" units="dimensionless"/>
<variable name="I_Na_tot" public_interface="in" units="uA_per_uF"/>
<variable name="I_K_tot" public_interface="in" units="uA_per_uF"/>
<variable name="I_Ca_tot" public_interface="in" units="uA_per_uF"/>
<variable name="I_leak" public_interface="in" units="mM_per_sec"/>
<variable name="I_rel" public_interface="in" units="mM_per_sec"/>
<variable name="I_up" public_interface="in" units="mM_per_sec"/>
<variable name="B_myo" public_interface="in" units="dimensionless"/>
<variable initial_value="-40" name="V_hold" units="mV"/>
<variable initial_value="-10" name="V_test" units="mV"/>
<variable name="V_clamp" units="mV"/>
<variable initial_value="0.02" name="R_clamp" units="ms"/>
<variable initial_value="-1e3" name="lambda" units="nFC_per_sAcm2"/>
<variable name="protocol" public_interface="in" units="dimensionless"/>
<variable name="I_pace" units="uA_per_uF"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_clamp</ci>
<piecewise>
<piece>
<ci>V_test</ci>
<apply>
<and/>
<apply>
<gt/>
<ci>time</ci>
<cn cellml:units="second">59.1</cn>
</apply>
<apply>
<lt/>
<ci>time</ci>
<cn cellml:units="second">59.5</cn>
</apply>
</apply>
</piece>
<otherwise>
<ci>V_hold</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>I_app</ci>
<piecewise>
<piece>
<cn cellml:units="dimensionless">0</cn>
<apply>
<eq/>
<ci>protocol</ci>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
<piece>
<ci>I_pace</ci>
<apply>
<eq/>
<ci>protocol</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</piece>
<otherwise>
<apply>
<divide/>
<apply>
<minus/>
<ci>V_clamp</ci>
<ci>V_m</ci>
</apply>
<ci>R_clamp</ci>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Na_i</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>lambda</ci>
<ci>I_Na_tot</ci>
<ci>A_Cap</ci>
</apply>
<apply>
<times/>
<ci>V_myo</ci>
<ci>z_Na</ci>
<ci>Frdy</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>K_i</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>lambda</ci>
<ci>I_K_tot</ci>
<ci>A_Cap</ci>
</apply>
<apply>
<times/>
<ci>V_myo</ci>
<ci>z_K</ci>
<ci>Frdy</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_i</ci>
</apply>
<apply>
<times/>
<ci>B_myo</ci>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>lambda</ci>
<ci>I_Ca_tot</ci>
<ci>A_Cap</ci>
</apply>
<apply>
<times/>
<ci>V_myo</ci>
<ci>z_Ca</ci>
<ci>Frdy</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>I_up</ci>
<ci>I_leak</ci>
</apply>
<ci>V_nsr</ci>
</apply>
<ci>V_myo</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>I_rel</ci>
<ci>V_jsr</ci>
</apply>
<ci>V_myo</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>V_m</ci>
</apply>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>I_Ca_tot</ci>
<ci>I_K_tot</ci>
<ci>I_Na_tot</ci>
</apply>
<ci>I_app</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>trel</ci>
</apply>
<piecewise>
<piece>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<times/>
<cn cellml:units="per_sec" type="e-notation">1<sep/>4</cn>
<ci>trel</ci>
</apply>
</apply>
<apply>
<gt/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>I_Ca_tot</ci>
<ci>I_K_tot</ci>
<ci>I_Na_tot</ci>
</apply>
<ci>I_app</ci>
</apply>
</apply>
<cn cellml:units="mV_per_sec" type="e-notation">30<sep/>3</cn>
</apply>
</piece>
<otherwise>
<cn cellml:units="dimensionless">1</cn>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>I_pace</ci>
<piecewise>
<piece>
<cn cellml:units="uA_per_uF">10</cn>
<apply>
<gt/>
<apply>
<sin/>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<pi/>
<ci>time</ci>
</apply>
</apply>
<cn cellml:units="dimensionless">0.9999</cn>
</apply>
</piece>
<otherwise>
<cn cellml:units="uA_per_uF">0</cn>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<connection>
<map_components component_1="environment" component_2="b1_AR_module"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="environment" component_2="cAMP_module"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="environment" component_2="PLB_module"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="environment" component_2="LCC_module"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="environment" component_2="Fast_Na_Current"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="environment" component_2="L_Type_Calcium_Current"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="environment" component_2="Transient_Outward_K_Current"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="environment" component_2="Steady_State_K_Current"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="environment" component_2="Other_SR_Fluxes_and_Concentrations"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="environment" component_2="Ion_Concentrations_and_Membrane_Potential"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="protocol" variable_2="protocol"/>
</connection>
<connection>
<map_components component_1="b1_AR_Gs_parameters" component_2="b1_AR_module"/>
<map_variables variable_1="L_totmax" variable_2="L_totmax"/>
<map_variables variable_1="sum_b1_AR" variable_2="sum_b1_AR"/>
<map_variables variable_1="Gs_tot" variable_2="Gs_tot"/>
<map_variables variable_1="Kl" variable_2="Kl"/>
<map_variables variable_1="Kr" variable_2="Kr"/>
<map_variables variable_1="Kc" variable_2="Kc"/>
<map_variables variable_1="k_bar_kp" variable_2="k_bar_kp"/>
<map_variables variable_1="k_bar_km" variable_2="k_bar_km"/>
<map_variables variable_1="k_p_kap" variable_2="k_p_kap"/>
<map_variables variable_1="k_p_kam" variable_2="k_p_kam"/>
<map_variables variable_1="k_g_act" variable_2="k_g_act"/>
<map_variables variable_1="k_hyd" variable_2="k_hyd"/>
<map_variables variable_1="k_reassoc" variable_2="k_reassoc"/>
</connection>
<connection>
<map_components component_1="cAMP_parameters" component_2="cAMP_module"/>
<map_variables variable_1="AC_tot" variable_2="AC_tot"/>
<map_variables variable_1="ATP" variable_2="ATP"/>
<map_variables variable_1="PDE_tot" variable_2="PDE_tot"/>
<map_variables variable_1="IBMX_tot" variable_2="IBMX_tot"/>
<map_variables variable_1="Fsk_tot" variable_2="Fsk_tot"/>
<map_variables variable_1="k_ac_basal" variable_2="k_ac_basal"/>
<map_variables variable_1="k_ac_gsa" variable_2="k_ac_gsa"/>
<map_variables variable_1="k_ac_fsk" variable_2="k_ac_fsk"/>
<map_variables variable_1="k_pde" variable_2="k_pde"/>
<map_variables variable_1="Km_basal" variable_2="Km_basal"/>
<map_variables variable_1="Km_gsa" variable_2="Km_gsa"/>
<map_variables variable_1="Km_fsk" variable_2="Km_fsk"/>
<map_variables variable_1="Km_pde" variable_2="Km_pde"/>
<map_variables variable_1="K_gsa" variable_2="K_gsa"/>
<map_variables variable_1="K_fsk" variable_2="K_fsk"/>
<map_variables variable_1="Ki_ibmx" variable_2="Ki_ibmx"/>
</connection>
<connection>
<map_components component_1="PKA_parameters" component_2="PKA_module"/>
<map_variables variable_1="PKAI_tot" variable_2="PKAI_tot"/>
<map_variables variable_1="PKAII_tot" variable_2="PKAII_tot"/>
<map_variables variable_1="PKI_tot" variable_2="PKI_tot"/>
<map_variables variable_1="K_a" variable_2="K_a"/>
<map_variables variable_1="K_b" variable_2="K_b"/>
<map_variables variable_1="K_d" variable_2="K_d"/>
<map_variables variable_1="Ki_pki" variable_2="Ki_pki"/>
</connection>
<connection>
<map_components component_1="PLB_parameters" component_2="PLB_module"/>
<map_variables variable_1="PLB_tot" variable_2="PLB_tot"/>
<map_variables variable_1="PP1_tot" variable_2="PP1_tot"/>
<map_variables variable_1="Inhib1_tot" variable_2="Inhib1_tot"/>
<map_variables variable_1="k_pka_plb" variable_2="k_pka_plb"/>
<map_variables variable_1="Km_pka_plb" variable_2="Km_pka_plb"/>
<map_variables variable_1="k_pp1_plb" variable_2="k_pp1_plb"/>
<map_variables variable_1="Km_pp1_plb" variable_2="Km_pp1_plb"/>
<map_variables variable_1="k_pka_i1" variable_2="k_pka_i1"/>
<map_variables variable_1="Km_pka_i1" variable_2="Km_pka_i1"/>
<map_variables variable_1="Vmax_pp2a_i1" variable_2="Vmax_pp2a_i1"/>
<map_variables variable_1="Km_pp2a_i1" variable_2="Km_pp2a_i1"/>
<map_variables variable_1="Ki_inhib1" variable_2="Ki_inhib1"/>
</connection>
<connection>
<map_components component_1="LCC_parameters" component_2="LCC_module"/>
<map_variables variable_1="epsilon" variable_2="epsilon"/>
<map_variables variable_1="LCC_tot" variable_2="LCC_tot"/>
<map_variables variable_1="PP1_lcc_tot" variable_2="PP1_lcc_tot"/>
<map_variables variable_1="PP2A_lcc_tot" variable_2="PP2A_lcc_tot"/>
<map_variables variable_1="k_pka_lcc" variable_2="k_pka_lcc"/>
<map_variables variable_1="Km_pka_lcc" variable_2="Km_pka_lcc"/>
<map_variables variable_1="k_pp1_lcc" variable_2="k_pp1_lcc"/>
<map_variables variable_1="Km_pp1_lcc" variable_2="Km_pp1_lcc"/>
<map_variables variable_1="k_pp2a_lcc" variable_2="k_pp2a_lcc"/>
<map_variables variable_1="Km_pp2a_lcc" variable_2="Km_pp2a_lcc"/>
</connection>
<connection>
<map_components component_1="EC_Coupling_Parameters" component_2="Nernst_Potentials"/>
<map_variables variable_1="Temp" variable_2="Temp"/>
<map_variables variable_1="Na_ext" variable_2="Na_ext"/>
<map_variables variable_1="K_ext" variable_2="K_ext"/>
<map_variables variable_1="Ca_ext" variable_2="Ca_ext"/>
</connection>
<connection>
<map_components component_1="EC_Coupling_Parameters" component_2="Fast_Na_Current"/>
<map_variables variable_1="G_Na" variable_2="G_Na"/>
</connection>
<connection>
<map_components component_1="EC_Coupling_Parameters" component_2="L_Type_Calcium_Current"/>
<map_variables variable_1="K_ext" variable_2="K_ext"/>
<map_variables variable_1="Ca_ext" variable_2="Ca_ext"/>
<map_variables variable_1="f" variable_2="f"/>
<map_variables variable_1="g" variable_2="g"/>
<map_variables variable_1="gamma_o" variable_2="gamma_o"/>
<map_variables variable_1="omega" variable_2="omega"/>
<map_variables variable_1="p_Ca" variable_2="p_Ca"/>
<map_variables variable_1="p_K" variable_2="p_K"/>
<map_variables variable_1="N_lcc" variable_2="N_lcc"/>
<map_variables variable_1="I_Ca05" variable_2="I_Ca05"/>
</connection>
<connection>
<map_components component_1="EC_Coupling_Parameters" component_2="Transient_Outward_K_Current"/>
<map_variables variable_1="G_to" variable_2="G_to"/>
</connection>
<connection>
<map_components component_1="EC_Coupling_Parameters" component_2="Steady_State_K_Current"/>
<map_variables variable_1="G_ss" variable_2="G_ss"/>
</connection>
<connection>
<map_components component_1="EC_Coupling_Parameters" component_2="Time_Independent_K_Current"/>
<map_variables variable_1="G_Ki_bar" variable_2="G_Ki_bar"/>
<map_variables variable_1="K_ext" variable_2="K_ext"/>
</connection>
<connection>
<map_components component_1="EC_Coupling_Parameters" component_2="Plateau_K_Current"/>
<map_variables variable_1="G_Kp" variable_2="G_Kp"/>
</connection>
<connection>
<map_components component_1="EC_Coupling_Parameters" component_2="Na_Ca_Exchanger_Current"/>
<map_variables variable_1="Na_ext" variable_2="Na_ext"/>
<map_variables variable_1="Ca_ext" variable_2="Ca_ext"/>
<map_variables variable_1="k_NaCa" variable_2="k_NaCa"/>
<map_variables variable_1="Km_Na" variable_2="Km_Na"/>
<map_variables variable_1="Km_Ca" variable_2="Km_Ca"/>
<map_variables variable_1="k_sat" variable_2="k_sat"/>
<map_variables variable_1="eta" variable_2="eta"/>
</connection>
<connection>
<map_components component_1="EC_Coupling_Parameters" component_2="Na_K_Pump_Current"/>
<map_variables variable_1="Na_ext" variable_2="Na_ext"/>
<map_variables variable_1="K_ext" variable_2="K_ext"/>
<map_variables variable_1="I_bar_NaK" variable_2="I_bar_NaK"/>
<map_variables variable_1="Km_Nai" variable_2="Km_Nai"/>
<map_variables variable_1="Km_Ko" variable_2="Km_Ko"/>
</connection>
<connection>
<map_components component_1="EC_Coupling_Parameters" component_2="Sarcolemmal_Ca_Pump_Current"/>
<map_variables variable_1="I_bar_PCa" variable_2="I_bar_PCa"/>
<map_variables variable_1="Km_PCa" variable_2="Km_PCa"/>
</connection>
<connection>
<map_components component_1="EC_Coupling_Parameters" component_2="Ca_Background_Current"/>
<map_variables variable_1="G_CaB" variable_2="G_CaB"/>
</connection>
<connection>
<map_components component_1="EC_Coupling_Parameters" component_2="Na_Background_Current"/>
<map_variables variable_1="G_NaB" variable_2="G_NaB"/>
</connection>
<connection>
<map_components component_1="EC_Coupling_Parameters" component_2="Calcium_Induced_Calcium_Release"/>
<map_variables variable_1="tau_on" variable_2="tau_on"/>
<map_variables variable_1="tau_off" variable_2="tau_off"/>
<map_variables variable_1="G_max_rel" variable_2="G_max_rel"/>
</connection>
<connection>
<map_components component_1="EC_Coupling_Parameters" component_2="Other_SR_Fluxes_and_Concentrations"/>
<map_variables variable_1="V_myo" variable_2="V_myo"/>
<map_variables variable_1="V_nsr" variable_2="V_nsr"/>
<map_variables variable_1="V_jsr" variable_2="V_jsr"/>
<map_variables variable_1="I_up_bar" variable_2="I_up_bar"/>
<map_variables variable_1="Km_up0" variable_2="Km_up0"/>
<map_variables variable_1="NSR_bar" variable_2="NSR_bar"/>
<map_variables variable_1="CSQN_bar" variable_2="CSQN_bar"/>
<map_variables variable_1="Km_CSQN" variable_2="Km_CSQN"/>
<map_variables variable_1="tau_tr" variable_2="tau_tr"/>
</connection>
<connection>
<map_components component_1="EC_Coupling_Parameters" component_2="Cytoplasmic_Calcium_Buffering"/>
<map_variables variable_1="TRPN_bar" variable_2="TRPN_bar"/>
<map_variables variable_1="CMDN_bar" variable_2="CMDN_bar"/>
<map_variables variable_1="INDO_bar" variable_2="INDO_bar"/>
<map_variables variable_1="Km_TRPN" variable_2="Km_TRPN"/>
<map_variables variable_1="Km_CMDN" variable_2="Km_CMDN"/>
<map_variables variable_1="Km_INDO" variable_2="Km_INDO"/>
</connection>
<connection>
<map_components component_1="EC_Coupling_Parameters" component_2="Ion_Concentrations_and_Membrane_Potential"/>
<map_variables variable_1="V_myo" variable_2="V_myo"/>
<map_variables variable_1="V_nsr" variable_2="V_nsr"/>
<map_variables variable_1="V_jsr" variable_2="V_jsr"/>
<map_variables variable_1="A_Cap" variable_2="A_Cap"/>
</connection>
<connection>
<map_components component_1="b1_AR_module" component_2="PKA_module"/>
<map_variables variable_1="PKAC_I" variable_2="PKAC_I"/>
</connection>
<connection>
<map_components component_1="cAMP_module" component_2="b1_AR_module"/>
<map_variables variable_1="Gs_agtp_tot" variable_2="Gs_agtp_tot"/>
</connection>
<connection>
<map_components component_1="cAMP_module" component_2="PKA_module"/>
<map_variables variable_1="cAMP_tot" variable_2="cAMP_tot"/>
<map_variables variable_1="cAMP" variable_2="cAMP"/>
</connection>
<connection>
<map_components component_1="PLB_module" component_2="PKA_module"/>
<map_variables variable_1="PKAC_I" variable_2="PKAC_I"/>
</connection>
<connection>
<map_components component_1="PLB_module" component_2="Other_SR_Fluxes_and_Concentrations"/>
<map_variables variable_1="frac_PLB" variable_2="frac_PLB"/>
<map_variables variable_1="frac_PLB_o" variable_2="frac_PLB_o"/>
</connection>
<connection>
<map_components component_1="LCC_module" component_2="PKA_module"/>
<map_variables variable_1="PKAC_II" variable_2="PKAC_II"/>
</connection>
<connection>
<map_components component_1="LCC_module" component_2="L_Type_Calcium_Current"/>
<map_variables variable_1="frac_LCCa_p" variable_2="frac_LCCa_p"/>
<map_variables variable_1="frac_LCCa_po" variable_2="frac_LCCa_po"/>
<map_variables variable_1="frac_LCCb_p" variable_2="frac_LCCb_p"/>
<map_variables variable_1="frac_LCCb_po" variable_2="frac_LCCb_po"/>
</connection>
<connection>
<map_components component_1="Nernst_Potentials" component_2="Fast_Na_Current"/>
<map_variables variable_1="E_Na" variable_2="E_Na"/>
</connection>
<connection>
<map_components component_1="Nernst_Potentials" component_2="L_Type_Calcium_Current"/>
<map_variables variable_1="Frdy" variable_2="Frdy"/>
<map_variables variable_1="FoRT" variable_2="FoRT"/>
</connection>
<connection>
<map_components component_1="Nernst_Potentials" component_2="Transient_Outward_K_Current"/>
<map_variables variable_1="E_K" variable_2="E_K"/>
</connection>
<connection>
<map_components component_1="Nernst_Potentials" component_2="Steady_State_K_Current"/>
<map_variables variable_1="E_K" variable_2="E_K"/>
</connection>
<connection>
<map_components component_1="Nernst_Potentials" component_2="Time_Independent_K_Current"/>
<map_variables variable_1="E_K" variable_2="E_K"/>
</connection>
<connection>
<map_components component_1="Nernst_Potentials" component_2="Plateau_K_Current"/>
<map_variables variable_1="E_K" variable_2="E_K"/>
</connection>
<connection>
<map_components component_1="Nernst_Potentials" component_2="Na_K_Pump_Current"/>
<map_variables variable_1="FoRT" variable_2="FoRT"/>
</connection>
<connection>
<map_components component_1="Nernst_Potentials" component_2="Ca_Background_Current"/>
<map_variables variable_1="E_Ca" variable_2="E_Ca"/>
</connection>
<connection>
<map_components component_1="Nernst_Potentials" component_2="Na_Background_Current"/>
<map_variables variable_1="E_Na" variable_2="E_Na"/>
</connection>
<connection>
<map_components component_1="Nernst_Potentials" component_2="Na_Ca_Exchanger_Current"/>
<map_variables variable_1="FoRT" variable_2="FoRT"/>
</connection>
<connection>
<map_components component_1="Nernst_Potentials" component_2="Ion_Concentrations_and_Membrane_Potential"/>
<map_variables variable_1="Frdy" variable_2="Frdy"/>
<map_variables variable_1="z_Na" variable_2="z_Na"/>
<map_variables variable_1="z_K" variable_2="z_K"/>
<map_variables variable_1="z_Ca" variable_2="z_Ca"/>
<map_variables variable_1="Na_i" variable_2="Na_i"/>
<map_variables variable_1="K_i" variable_2="K_i"/>
<map_variables variable_1="Ca_i" variable_2="Ca_i"/>
</connection>
<connection>
<map_components component_1="Total_Membrane_Currents" component_2="Fast_Na_Current"/>
<map_variables variable_1="I_Na" variable_2="I_Na"/>
</connection>
<connection>
<map_components component_1="Total_Membrane_Currents" component_2="L_Type_Calcium_Current"/>
<map_variables variable_1="I_Ca" variable_2="I_Ca"/>
<map_variables variable_1="I_CaK" variable_2="I_CaK"/>
</connection>
<connection>
<map_components component_1="Total_Membrane_Currents" component_2="Transient_Outward_K_Current"/>
<map_variables variable_1="I_to" variable_2="I_to"/>
</connection>
<connection>
<map_components component_1="Total_Membrane_Currents" component_2="Steady_State_K_Current"/>
<map_variables variable_1="I_ss" variable_2="I_ss"/>
</connection>
<connection>
<map_components component_1="Total_Membrane_Currents" component_2="Time_Independent_K_Current"/>
<map_variables variable_1="I_Ki" variable_2="I_Ki"/>
</connection>
<connection>
<map_components component_1="Total_Membrane_Currents" component_2="Plateau_K_Current"/>
<map_variables variable_1="I_Kp" variable_2="I_Kp"/>
</connection>
<connection>
<map_components component_1="Total_Membrane_Currents" component_2="Na_Ca_Exchanger_Current"/>
<map_variables variable_1="I_NCX" variable_2="I_NCX"/>
</connection>
<connection>
<map_components component_1="Total_Membrane_Currents" component_2="Na_K_Pump_Current"/>
<map_variables variable_1="I_NaK" variable_2="I_NaK"/>
</connection>
<connection>
<map_components component_1="Total_Membrane_Currents" component_2="Sarcolemmal_Ca_Pump_Current"/>
<map_variables variable_1="I_PCa" variable_2="I_PCa"/>
</connection>
<connection>
<map_components component_1="Total_Membrane_Currents" component_2="Ca_Background_Current"/>
<map_variables variable_1="I_CaB" variable_2="I_CaB"/>
</connection>
<connection>
<map_components component_1="Total_Membrane_Currents" component_2="Na_Background_Current"/>
<map_variables variable_1="I_NaB" variable_2="I_NaB"/>
</connection>
<connection>
<map_components component_1="Total_Membrane_Currents" component_2="Calcium_Induced_Calcium_Release"/>
<map_variables variable_1="I_Ca_tot" variable_2="I_Ca_tot"/>
</connection>
<connection>
<map_components component_1="Total_Membrane_Currents" component_2="Ion_Concentrations_and_Membrane_Potential"/>
<map_variables variable_1="I_Na_tot" variable_2="I_Na_tot"/>
<map_variables variable_1="I_K_tot" variable_2="I_K_tot"/>
<map_variables variable_1="I_Ca_tot" variable_2="I_Ca_tot"/>
</connection>
<connection>
<map_components component_1="Other_SR_Fluxes_and_Concentrations" component_2="Calcium_Induced_Calcium_Release"/>
<map_variables variable_1="I_rel" variable_2="I_rel"/>
<map_variables variable_1="Ca_jsr" variable_2="Ca_jsr"/>
</connection>
<connection>
<map_components component_1="Ion_Concentrations_and_Membrane_Potential" component_2="Fast_Na_Current"/>
<map_variables variable_1="V_m" variable_2="V_m"/>
</connection>
<connection>
<map_components component_1="Ion_Concentrations_and_Membrane_Potential" component_2="Transient_Outward_K_Current"/>
<map_variables variable_1="V_m" variable_2="V_m"/>
</connection>
<connection>
<map_components component_1="Ion_Concentrations_and_Membrane_Potential" component_2="Steady_State_K_Current"/>
<map_variables variable_1="V_m" variable_2="V_m"/>
</connection>
<connection>
<map_components component_1="Ion_Concentrations_and_Membrane_Potential" component_2="Time_Independent_K_Current"/>
<map_variables variable_1="V_m" variable_2="V_m"/>
</connection>
<connection>
<map_components component_1="Ion_Concentrations_and_Membrane_Potential" component_2="Plateau_K_Current"/>
<map_variables variable_1="V_m" variable_2="V_m"/>
</connection>
<connection>
<map_components component_1="Ion_Concentrations_and_Membrane_Potential" component_2="Ca_Background_Current"/>
<map_variables variable_1="V_m" variable_2="V_m"/>
</connection>
<connection>
<map_components component_1="Ion_Concentrations_and_Membrane_Potential" component_2="Na_Background_Current"/>
<map_variables variable_1="V_m" variable_2="V_m"/>
</connection>
<connection>
<map_components component_1="Ion_Concentrations_and_Membrane_Potential" component_2="Calcium_Induced_Calcium_Release"/>
<map_variables variable_1="I_rel" variable_2="I_rel"/>
<map_variables variable_1="Ca_i" variable_2="Ca_i"/>
<map_variables variable_1="trel" variable_2="trel"/>
</connection>
<connection>
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<title xmlns="http://cellml.org/tmp-documentation">Modelling Beta-adrenergic Control of Cardiac Myocyte Contractility in Silico</title>
<author xmlns="http://cellml.org/tmp-documentation">
<firstname xmlns="http://cellml.org/tmp-documentation">Catherine</firstname>
<surname xmlns="http://cellml.org/tmp-documentation">Lloyd</surname>
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<shortaffil xmlns="http://cellml.org/tmp-documentation">Auckland Bioengineering Institute, The University of Auckland</shortaffil>
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This CellML version of the Saucerman and McCulloch 2003 model is a translation of Jeff Saucerman's original MATLAB code, where all figures of the original paper are reproduced.
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ABSTRACT: The beta-adrenergic signaling pathway regulates cardiac myocyte contractility through a combination of feedforward and feedback mechanisms. We used systems analysis to investigate how the components and topology of this signaling network permit neurohormonal control of excitation-contraction coupling in the rat ventricular myocyte. A kinetic model integrating beta-adrenergic signaling with excitation-contraction coupling was formulated, and each subsystem was validated with independent biochemical and physiological measurements. Model analysis was used to investigate quantitatively the effects of specific molecular perturbations. 3-Fold overexpression of adenylyl cyclase in the model allowed an 85% higher rate of cyclic AMP synthesis than an equivalent overexpression of beta 1-adrenergic receptor, and manipulating the affinity of Gs alpha for adenylyl cyclase was a more potent regulator of cyclic AMP production. The model predicted that less than 40% of adenylyl cyclase molecules may be stimulated under maximal receptor activation, and an experimental protocol is suggested for validating this prediction. The model also predicted that the endogenous heat-stable protein kinase inhibitor may enhance basal cyclic AMP buffering by 68% and increasing the apparent Hill coefficient of protein kinase A activation from 1.0 to 2.0. Finally, phosphorylation of the L-type calcium channel and phospholamban were found sufficient to predict the dominant changes in myocyte contractility, including a 2.6x increase in systolic calcium (inotropy) and a 28% decrease in calcium half-relaxation time (lusitropy). By performing systems analysis, the consequences of molecular perturbations in the beta-adrenergic signaling network may be understood within the context of integrative cellular physiology.
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The original paper reference is cited below:
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<para xmlns="http://cellml.org/tmp-documentation">Modeling beta-adrenergic control of cardiac myocyte contractility <emphasis xmlns="http://cellml.org/tmp-documentation">in silico</emphasis>
, Jeffrey J. Saucerman, Laurence L. Brunton, Anushka P. Michailova, and Andrew D. McCulloch, 2003, <emphasis xmlns="http://cellml.org/tmp-documentation">Journal of Biological Chemistry</emphasis>, 48, 47997-48003. <ulink xmlns="http://cellml.org/tmp-documentation" url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12972422&dopt=Abstract">PubMed ID: 12972422</ulink>
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<caption xmlns="http://cellml.org/tmp-documentation">Schematic diagram of the integrated model components, including the beta-adrenergic network, calcium handling, and the electrophysiology of the rat ventricular myocyte.</caption>
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