- Author:
- Fariba <fbir042@aucklanduni.ac.nz>
- Date:
- 2025-02-19 21:55:52+13:00
- Desc:
- Second Commit
- Permanent Source URI:
- https://staging.physiomeproject.org/workspace/b36/rawfile/5e6492173917e6493bb53402aa50e0eb3562601b/Main_Coupled_SMC_Model.cellml
<?xml version='1.0' encoding='UTF-8'?>
<model name="Hai" xmlns="http://www.cellml.org/cellml/1.1#" xmlns:cellml="http://www.cellml.org/cellml/1.1#" xmlns:xlink="http://www.w3.org/1999/xlink">
<import xlink:href="EC_SMC_Units.cellml">
<units name="C_per_mol" units_ref="C_per_mol"/>
<units name="first_order_rate_constant" units_ref="first_order_rate_constant"/>
<units name="mJ_per_K_per_mol" units_ref="mJ_per_K_per_mol"/>
<units name="M_per_cmsq" units_ref="M_per_cmsq"/>
<units name="mV" units_ref="mV"/>
<units name="per_sec" units_ref="per_sec"/>
<units name="per_uM" units_ref="per_uM"/>
<units name="per_uM2" units_ref="per_uM2"/>
<units name="per_uM_per_sec" units_ref="per_uM_per_sec"/>
<units name="uM" units_ref="uM"/>
<units name="nS_per_uM" units_ref="nS_per_uM"/>
<units name="uA_per_cmsq" units_ref="uA_per_cmsq"/>
<units name="uM2" units_ref="uM2"/>
<units name="umol_per_cmsq" units_ref="umol_per_cmsq"/>
<units name="uM_per_sec" units_ref="uM_per_sec"/>
</import>
<import xlink:href="Intracellular_Calcium_SMC.cellml">
<component component_ref="asm_ca" name="asm_ca"/>
<component component_ref="ca_parameters" name="ca_parameters"/>
<component component_ref="calcium" name="calcium"/>
</import>
<import xlink:href="NO_cGMP_Signalling_SMC.cellml">
<component component_ref="sGC_SMC" name="sGC_SMC"/>
</import>
<import xlink:href="Coupled_Main_EC_Model.cellml">
<component component_ref="Activation_of_G_proteins" name="Activation_of_G_proteins"/>
<component component_ref="Activation_of_protein_kinases" name="Activation_of_protein_kinases"/>
<component component_ref="Calcium_signalling" name="Calcium_signalling"/>
<component component_ref="NO_production" name="NO_production"/>
<component component_ref="Phosphorylation_and_formation_of_eNOS_complexes" name="Phosphorylation_and_formation_of_eNOS_complexes"/>
</import>
<component name="Environment">
<variable initial_value="12" name="tau" public_interface="out" units="dimensionless"/>
<variable name="time" public_interface="out" units="second"/>
</component>
<component name="SMC_Par">
<variable name="Ca_in_SMC" public_interface="in" units="uM"/>
<variable name="Ca_SR" public_interface="in" units="uM"/>
<variable name="Ca_t" public_interface="in" units="uM"/>
<variable name="I_ca" public_interface="in" units="uA_per_cmsq"/>
<variable name="J_release" public_interface="in" units="uM_per_sec"/>
<variable name="J_serca" public_interface="in" units="uM_per_sec"/>
<variable name="J_in" public_interface="in" units="uM_per_sec"/>
<variable name="J_pm" public_interface="in" units="uM_per_sec"/>
<variable name="k_mlcpb" public_interface="in" units="per_sec"/>
<variable name="k_mlcpc" public_interface="in" units="per_sec"/>
<variable name="k_mlcpm" public_interface="in" units="uM"/>
<variable name="P" public_interface="in" units="dimensionless"/>
<variable name="p_agonist" public_interface="in" units="uM"/>
<variable name="P_ipr" public_interface="in" units="dimensionless"/>
<variable name="P_RyR" public_interface="in" units="dimensionless"/>
<variable name="V_ca" public_interface="in" units="mV"/>
</component>
<component name="NO_sGC">
<variable name="All_E5c" public_interface="in" units="uM_per_sec"/>
<variable name="cGMP_EC" public_interface="in" units="uM"/>
<variable name="cGMP_SMC" public_interface="in" units="uM"/>
<variable name="E5c" public_interface="in" units="dimensionless"/>
<variable name="E6c" public_interface="in" units="dimensionless"/>
<variable name="Eb" public_interface="in" units="dimensionless"/>
<variable name="eNOS_CaM" public_interface="in" units="uM"/>
<variable name="eNOS_CaM_star" public_interface="in" units="uM"/>
<variable name="h2" public_interface="in" units="uM_per_sec"/>
<variable name="h3" public_interface="in" units="uM_per_sec"/>
<variable name="h_4" public_interface="in" units="uM_per_sec"/>
<variable name="h_four" public_interface="in" units="per_sec"/>
<variable name="J_dif" public_interface="out" units="uM_per_sec"/>
<variable name="J_no" public_interface="in" units="uM_per_sec"/>
<variable initial_value="0.1" name="k_dif" units="uM_per_sec"/>
<variable name="Km_pde" public_interface="in" units="uM"/>
<variable name="K_pde" public_interface="in" units="per_sec"/>
<variable name="n_cGMPS" public_interface="in" units="dimensionless"/>
<variable name="n_EC" public_interface="in" units="dimensionless"/>
<variable name="n_mlcph" public_interface="in" units="dimensionless"/>
<variable name="NO_EC" public_interface="in" units="uM"/>
<variable name="NO_SMC" public_interface="in" units="uM"/>
<variable name="Q_sGC" public_interface="in" units="uM_per_sec"/>
<variable name="Q_NO" public_interface="in" units="uM_per_sec"/>
<variable name="vd" public_interface="in" units="uM_per_sec"/>
<variable name="vp" public_interface="in" units="uM_per_sec"/>
<!-- var vp_EC: per_sec;-->
<variable name="vpvd" units="uM_per_sec"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>J_dif</ci>
<apply>
<times/>
<ci>k_dif</ci>
<apply>
<minus/>
<ci>NO_EC</ci>
<ci>NO_SMC</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>vpvd</ci>
<apply>
<minus/>
<ci>vp</ci>
<ci>vd</ci>
</apply>
</apply>
</math>
<!-- vp_EC = 1.26{uM_per_sec}*(4.8e-06{uM2}+0.03533{uM}*NO_EC+sqr(NO_EC))/(0.00120016{uM2}+0.03733{uM}*NO_EC+sqr(NO_EC));-->
</component>
<component name="kay2">
<variable name="k1a" public_interface="in" units="per_sec"/>
<variable name="k2" public_interface="out" units="per_sec"/>
<variable name="k2y" public_interface="in" units="per_sec"/>
<variable name="k2h" public_interface="in" units="per_sec"/>
<variable initial_value="0.88" name="k3" public_interface="out" units="first_order_rate_constant"/>
<variable name="k_dno" public_interface="in" units="per_sec"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>k2</ci>
<apply>
<plus/>
<ci>k2h</ci>
<ci>k2y</ci>
</apply>
</apply>
</math>
</component>
<component name="M">
<variable name="AM" public_interface="in" units="dimensionless"/>
<variable initial_value="1" name="M" public_interface="out" units="dimensionless"/>
<variable name="Mp" public_interface="in" units="dimensionless"/>
<variable name="k1" public_interface="in" units="first_order_rate_constant"/>
<variable name="k2" public_interface="in" units="first_order_rate_constant"/>
<variable name="k7" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>M</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>k1</ci>
</apply>
<ci>M</ci>
</apply>
<apply>
<times/>
<ci>k2</ci>
<ci>Mp</ci>
</apply>
<apply>
<times/>
<ci>k7</ci>
<ci>AM</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Mp">
<variable name="AMp" public_interface="in" units="dimensionless"/>
<variable initial_value="0" name="Mp" public_interface="out" units="dimensionless"/>
<variable name="M" public_interface="in" units="dimensionless"/>
<variable name="k1" public_interface="in" units="first_order_rate_constant"/>
<variable name="k2" public_interface="in" units="first_order_rate_constant"/>
<variable name="k3" public_interface="in" units="first_order_rate_constant"/>
<variable name="k4" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Mp</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>k4</ci>
<ci>AMp</ci>
</apply>
<apply>
<times/>
<ci>k1</ci>
<ci>M</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>k2</ci>
<ci>k3</ci>
</apply>
<ci>Mp</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="AMp">
<variable name="AM" public_interface="in" units="dimensionless"/>
<variable initial_value="0" name="AMp" public_interface="out" units="dimensionless"/>
<variable name="Mp" public_interface="in" units="dimensionless"/>
<variable name="k5" public_interface="in" units="first_order_rate_constant"/>
<variable name="k6" public_interface="in" units="first_order_rate_constant"/>
<variable name="k3" public_interface="in" units="first_order_rate_constant"/>
<variable name="k4" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>AMp</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>k3</ci>
<ci>Mp</ci>
</apply>
<apply>
<times/>
<ci>k6</ci>
<ci>AM</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>k4</ci>
<ci>k5</ci>
</apply>
<ci>AMp</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="AM">
<variable initial_value="0" name="AM" public_interface="out" units="dimensionless"/>
<variable name="AMp" public_interface="in" units="dimensionless"/>
<variable name="k5" public_interface="in" units="first_order_rate_constant"/>
<variable name="k6" public_interface="in" units="first_order_rate_constant"/>
<variable name="k7" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>AM</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k5</ci>
<ci>AMp</ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>k6</ci>
<ci>k7</ci>
</apply>
<ci>AM</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="phosphorylation">
<variable name="AMp" public_interface="in" units="dimensionless"/>
<variable name="Mp" public_interface="in" units="dimensionless"/>
<variable name="phosphorylation" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>phosphorylation</ci>
<apply>
<plus/>
<ci>AMp</ci>
<ci>Mp</ci>
</apply>
</apply>
</math>
</component>
<component name="stress">
<variable name="AMp" public_interface="in" units="dimensionless"/>
<variable name="AM" public_interface="in" units="dimensionless"/>
<variable name="stress" public_interface="out" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>stress</ci>
<apply>
<plus/>
<ci>AMp</ci>
<ci>AM</ci>
</apply>
</apply>
</math>
</component>
<component name="model_parameters1">
<variable name="k1" public_interface="in" units="first_order_rate_constant"/>
<variable name="k2" public_interface="in" units="first_order_rate_constant"/>
<variable name="k5" public_interface="out" units="first_order_rate_constant"/>
<variable name="k6" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.22" name="k4" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.12" name="k7" public_interface="out" units="first_order_rate_constant"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>k6</ci>
<ci>k1</ci>
</apply>
<apply>
<eq/>
<ci>k5</ci>
<ci>k2</ci>
</apply>
</math>
</component>
<component name="EC_par">
<variable name="a_0" public_interface="in" units="uM2"/>
<variable name="a_1" public_interface="in" units="uM"/>
<variable name="AKT_star" public_interface="in" units="uM"/>
<variable name="AKT_tot" public_interface="in" units="uM"/>
<variable name="All_NO" public_interface="in" units="uM_per_sec"/>
<variable name="alpha" public_interface="in" units="per_sec"/>
<variable name="a_PI3K" public_interface="in" units="dimensionless"/>
<variable name="b_0" public_interface="in" units="dimensionless"/>
<variable name="b_1" public_interface="in" units="uM"/>
<variable name="B_tot" public_interface="in" units="uM"/>
<variable name="beta" public_interface="in" units="dimensionless"/>
<variable name="Ca2_c" public_interface="in" units="uM"/>
<variable name="Ca2_b" public_interface="in" units="uM"/>
<variable name="Ca2_e" public_interface="in" units="uM"/>
<variable name="Ca2_s0" public_interface="in" units="uM"/>
<variable name="Ca2_s" public_interface="in" units="uM"/>
<variable name="Ca4_CaM" public_interface="in" units="uM"/>
<variable name="CaM_tot" public_interface="in" units="uM"/>
<variable name="cGMP_EC" public_interface="in" units="uM"/>
<variable name="delta" public_interface="in" units="dimensionless"/>
<variable name="eNOS_CaM" public_interface="in" units="uM"/>
<variable name="eNOS_CaM_star" public_interface="in" units="uM"/>
<variable name="eNOS_Cav" public_interface="in" units="uM"/>
<variable name="eNOS_Cav_0" public_interface="in" units="uM"/>
<variable name="eNOS_tot" public_interface="in" units="uM"/>
<variable name="eta" public_interface="in" units="per_sec"/>
<variable name="G" public_interface="in" units="uM"/>
<variable name="g_0" public_interface="in" units="uM2"/>
<variable name="g_1" public_interface="in" units="uM"/>
<variable name="Gt" public_interface="in" units="uM"/>
<variable name="IP3" public_interface="in" units="uM"/>
<variable name="k_1p" public_interface="in" units="per_sec"/>
<variable name="k_2" public_interface="in" units="uM"/>
<variable name="k_2p" public_interface="in" units="per_sec"/>
<variable name="k_3" public_interface="in" units="uM"/>
<variable name="k_5" public_interface="in" units="uM"/>
<variable name="k_a" public_interface="in" units="per_sec"/>
<variable name="k_AKT_negative" public_interface="in" units="per_sec"/>
<variable name="k_AKT_positive" public_interface="in" units="per_sec"/>
<variable name="k_Ca4_CaM" public_interface="in" units="per_sec"/>
<variable name="k_CaM_negative" public_interface="in" units="per_sec"/>
<variable name="k_CaM_positive" public_interface="in" units="per_sec"/>
<variable name="k_CCE" public_interface="in" units="per_sec"/>
<variable name="k_cGMP" public_interface="in" units="uM"/>
<variable name="K_cp" public_interface="in" units="per_uM"/>
<variable name="k_d" public_interface="in" units="per_sec"/>
<variable name="k_dCaM" public_interface="in" units="dimensionless"/>
<variable name="k_eAKT_max" public_interface="in" units="per_sec"/>
<variable name="k_eAKT_negative" public_interface="in" units="per_sec"/>
<variable name="k_eAKT_positive" public_interface="in" units="per_sec"/>
<variable name="k_half_CaM" public_interface="in" units="uM"/>
<variable name="k_leak" public_interface="in" units="per_uM_per_sec"/>
<variable name="k_mNO" public_interface="in" units="uM"/>
<variable name="k_off" public_interface="in" units="per_sec"/>
<variable name="k_on" public_interface="in" units="per_uM_per_sec"/>
<variable name="k_out" public_interface="in" units="uM_per_sec"/>
<variable name="k_PIP2_negative" public_interface="in" units="per_sec"/>
<variable name="k_PIP2_positive" public_interface="in" units="per_sec"/>
<variable name="k_PKC_negative" public_interface="in" units="per_sec"/>
<variable name="k_PKC_positive" public_interface="in" units="per_sec"/>
<variable name="k_rel" public_interface="in" units="per_sec"/>
<variable name="k_res" public_interface="in" units="uM_per_sec"/>
<variable name="k_Thr_negative" public_interface="in" units="per_sec"/>
<variable name="k_Thr_positive" public_interface="in" units="per_sec"/>
<variable name="lambda" public_interface="in" units="dimensionless"/>
<variable name="lambda_NO" public_interface="in" units="per_sec"/>
<variable name="m_1" public_interface="in" units="per_uM"/>
<variable name="M_ATP" public_interface="in" units="dimensionless"/>
<variable name="mu1" public_interface="in" units="per_sec"/>
<variable name="N" public_interface="in" units="dimensionless"/>
<variable name="NO_d" public_interface="in" units="uM_per_sec"/>
<variable name="NO_EC" public_interface="in" units="uM"/>
<variable name="O2" public_interface="in" units="uM"/>
<variable name="Phi" public_interface="in" units="dimensionless"/>
<variable name="PIP2" public_interface="in" units="uM"/>
<variable name="PIP2_t" public_interface="in" units="uM"/>
<variable name="PIP3" public_interface="in" units="uM"/>
<variable name="PIP3_max" public_interface="in" units="uM"/>
<variable name="PIP3_min" public_interface="in" units="uM"/>
<variable name="PIP2_tot" public_interface="in" units="uM"/>
<variable name="PKC_star" public_interface="in" units="uM"/>
<variable name="PKC_tot" public_interface="in" units="uM"/>
<variable name="psi" public_interface="in" units="per_uM"/>
<variable name="q_CCE" public_interface="in" units="uM_per_sec"/>
<variable name="q_in" public_interface="in" units="uM_per_sec"/>
<variable name="q_max" public_interface="in" units="uM_per_sec"/>
<variable name="q_MSIC" public_interface="in" units="uM_per_sec"/>
<variable name="Q_NO" public_interface="in" units="uM_per_sec"/>
<variable name="q_out" public_interface="in" units="uM_per_sec"/>
<variable name="q_rel" public_interface="in" units="uM_per_sec"/>
<variable name="q_res" public_interface="in" units="uM_per_sec"/>
<variable name="Q_sGC" public_interface="in" units="uM_per_sec"/>
<variable name="r" public_interface="in" units="per_sec"/>
<variable name="r_f" public_interface="in" units="per_sec"/>
<variable name="R_NO_max" public_interface="in" units="per_sec"/>
<variable name="r_r" public_interface="in" units="per_sec"/>
<variable name="R_star" public_interface="in" units="dimensionless"/>
<variable name="sGC" public_interface="in" units="uM"/>
<variable name="theta" public_interface="in" units="dimensionless"/>
<variable name="v_cGMP_max" public_interface="in" units="uM_per_sec"/>
<variable name="v_r" public_interface="in" units="dimensionless"/>
<variable name="W" public_interface="in" units="dimensionless"/>
<variable name="W_0" public_interface="in" units="dimensionless"/>
<variable name="X" public_interface="in" units="per_sec"/>
<variable name="xi" public_interface="in" units="per_uM2"/>
<variable name="Z" public_interface="in" units="dimensionless"/>
</component>
<connection>
<map_components component_1="sGC_SMC" component_2="NO_sGC"/>
<map_variables variable_1="Eb" variable_2="Eb"/>
<map_variables variable_1="E5c" variable_2="E5c"/>
<map_variables variable_1="E6c" variable_2="E6c"/>
<map_variables variable_1="NO_SMC" variable_2="NO_SMC"/>
<map_variables variable_1="cGMP_SMC" variable_2="cGMP_SMC"/>
<map_variables variable_1="vd" variable_2="vd"/>
<map_variables variable_1="vp" variable_2="vp"/>
<map_variables variable_1="J_dif" variable_2="J_dif"/>
<map_variables variable_1="n_mlcph" variable_2="n_mlcph"/>
<map_variables variable_1="h3" variable_2="h3"/>
<map_variables variable_1="h2" variable_2="h2"/>
<map_variables variable_1="h_4" variable_2="h_4"/>
<map_variables variable_1="All_E5c" variable_2="All_E5c"/>
<map_variables variable_1="n_EC" variable_2="n_EC"/>
<map_variables variable_1="h_four" variable_2="h_four"/>
<map_variables variable_1="J_no" variable_2="J_no"/>
<map_variables variable_1="n_cGMPS" variable_2="n_cGMPS"/>
<map_variables variable_1="Km_pde" variable_2="Km_pde"/>
<map_variables variable_1="K_pde" variable_2="K_pde"/>
</connection>
<connection>
<map_components component_1="calcium" component_2="asm_ca"/>
<map_variables variable_1="Ca_in_SMC" variable_2="Ca_in_SMC"/>
<map_variables variable_1="p_agonist" variable_2="p_agonist"/>
</connection>
<connection>
<map_components component_1="asm_ca" component_2="SMC_Par"/>
<map_variables variable_1="Ca_in_SMC" variable_2="Ca_in_SMC"/>
<map_variables variable_1="Ca_SR" variable_2="Ca_SR"/>
<map_variables variable_1="Ca_t" variable_2="Ca_t"/>
<map_variables variable_1="p_agonist" variable_2="p_agonist"/>
<map_variables variable_1="J_release" variable_2="J_release"/>
<map_variables variable_1="J_serca" variable_2="J_serca"/>
<map_variables variable_1="J_in" variable_2="J_in"/>
<map_variables variable_1="J_pm" variable_2="J_pm"/>
<map_variables variable_1="V_ca" variable_2="V_ca"/>
<map_variables variable_1="P_ipr" variable_2="P_ipr"/>
<map_variables variable_1="P_RyR" variable_2="P_RyR"/>
<map_variables variable_1="I_ca" variable_2="I_ca"/>
</connection>
<connection>
<map_components component_1="calcium" component_2="model_parameters1"/>
<map_variables variable_1="k1" variable_2="k1"/>
</connection>
<connection>
<map_components component_1="kay2" component_2="model_parameters1"/>
<map_variables variable_1="k2" variable_2="k2"/>
</connection>
<connection>
<map_components component_1="sGC_SMC" component_2="kay2"/>
<map_variables variable_1="k2y" variable_2="k2y"/>
<map_variables variable_1="k_dno" variable_2="k_dno"/>
</connection>
<connection>
<map_components component_1="SMC_Par" component_2="calcium"/>
<map_variables variable_1="P" variable_2="P"/>
</connection>
<connection>
<map_components component_1="SMC_Par" component_2="sGC_SMC"/>
<map_variables variable_1="k_mlcpb" variable_2="k_mlcpb"/>
<map_variables variable_1="k_mlcpc" variable_2="k_mlcpc"/>
<map_variables variable_1="k_mlcpm" variable_2="k_mlcpm"/>
</connection>
<connection>
<map_components component_1="calcium" component_2="kay2"/>
<map_variables variable_1="k2h" variable_2="k2h"/>
<map_variables variable_1="k1a" variable_2="k1a"/>
</connection>
<connection>
<map_components component_1="M" component_2="Environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Mp" component_2="Environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="AMp" component_2="Environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="AM" component_2="Environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Environment" component_2="calcium"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Environment" component_2="asm_ca"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Environment" component_2="sGC_SMC"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="M" component_2="model_parameters1"/>
<map_variables variable_1="k7" variable_2="k7"/>
</connection>
<connection>
<map_components component_1="M" component_2="model_parameters1"/>
<map_variables variable_1="k1" variable_2="k1"/>
</connection>
<connection>
<map_components component_1="M" component_2="kay2"/>
<map_variables variable_1="k2" variable_2="k2"/>
</connection>
<connection>
<map_components component_1="Mp" component_2="model_parameters1"/>
<map_variables variable_1="k4" variable_2="k4"/>
</connection>
<connection>
<map_components component_1="Mp" component_2="model_parameters1"/>
<map_variables variable_1="k1" variable_2="k1"/>
</connection>
<connection>
<map_components component_1="Mp" component_2="kay2"/>
<map_variables variable_1="k2" variable_2="k2"/>
</connection>
<connection>
<map_components component_1="AMp" component_2="model_parameters1"/>
<map_variables variable_1="k5" variable_2="k5"/>
<map_variables variable_1="k6" variable_2="k6"/>
<map_variables variable_1="k4" variable_2="k4"/>
</connection>
<connection>
<map_components component_1="AM" component_2="model_parameters1"/>
<map_variables variable_1="k5" variable_2="k5"/>
<map_variables variable_1="k6" variable_2="k6"/>
<map_variables variable_1="k7" variable_2="k7"/>
</connection>
<connection>
<map_components component_1="AM" component_2="M"/>
<map_variables variable_1="AM" variable_2="AM"/>
</connection>
<connection>
<map_components component_1="AM" component_2="AMp"/>
<map_variables variable_1="AMp" variable_2="AMp"/>
<map_variables variable_1="AM" variable_2="AM"/>
</connection>
<connection>
<map_components component_1="M" component_2="Mp"/>
<map_variables variable_1="M" variable_2="M"/>
<map_variables variable_1="Mp" variable_2="Mp"/>
</connection>
<connection>
<map_components component_1="Mp" component_2="AMp"/>
<map_variables variable_1="Mp" variable_2="Mp"/>
<map_variables variable_1="AMp" variable_2="AMp"/>
</connection>
<connection>
<map_components component_1="phosphorylation" component_2="AMp"/>
<map_variables variable_1="AMp" variable_2="AMp"/>
</connection>
<connection>
<map_components component_1="phosphorylation" component_2="Mp"/>
<map_variables variable_1="Mp" variable_2="Mp"/>
</connection>
<connection>
<map_components component_1="stress" component_2="AMp"/>
<map_variables variable_1="AMp" variable_2="AMp"/>
</connection>
<connection>
<map_components component_1="stress" component_2="AM"/>
<map_variables variable_1="AM" variable_2="AM"/>
</connection>
<connection>
<map_components component_1="Environment" component_2="Activation_of_G_proteins"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="tau" variable_2="tau"/>
</connection>
<connection>
<map_components component_1="Environment" component_2="Calcium_signalling"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="tau" variable_2="tau"/>
</connection>
<connection>
<map_components component_1="Environment" component_2="Activation_of_protein_kinases"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="tau" variable_2="tau"/>
</connection>
<connection>
<map_components component_1="Environment" component_2="Phosphorylation_and_formation_of_eNOS_complexes"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Environment" component_2="NO_production"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Activation_of_G_proteins" component_2="Calcium_signalling"/>
<map_variables variable_1="IP3" variable_2="IP3"/>
</connection>
<connection>
<map_components component_1="NO_production" component_2="Calcium_signalling"/>
<map_variables variable_1="cGMP_EC" variable_2="cGMP_EC"/>
</connection>
<connection>
<map_components component_1="Activation_of_G_proteins" component_2="Activation_of_protein_kinases"/>
<map_variables variable_1="k_PIP2_positive" variable_2="k_PIP2_positive"/>
<map_variables variable_1="PIP3" variable_2="PIP3"/>
</connection>
<connection>
<map_components component_1="Phosphorylation_and_formation_of_eNOS_complexes" component_2="NO_production"/>
<map_variables variable_1="eNOS_CaM" variable_2="eNOS_CaM"/>
<map_variables variable_1="eNOS_CaM_star" variable_2="eNOS_CaM_star"/>
</connection>
<connection>
<map_components component_1="Phosphorylation_and_formation_of_eNOS_complexes" component_2="Calcium_signalling"/>
<map_variables variable_1="Ca2_c" variable_2="Ca2_c"/>
</connection>
<connection>
<map_components component_1="Phosphorylation_and_formation_of_eNOS_complexes" component_2="Activation_of_protein_kinases"/>
<map_variables variable_1="AKT_star" variable_2="AKT_star"/>
<map_variables variable_1="AKT_tot" variable_2="AKT_tot"/>
<map_variables variable_1="PKC_tot" variable_2="PKC_tot"/>
<map_variables variable_1="PKC_star" variable_2="PKC_star"/>
</connection>
<connection>
<map_components component_1="NO_sGC" component_2="NO_production"/>
<map_variables variable_1="NO_EC" variable_2="NO_EC"/>
<map_variables variable_1="Q_NO" variable_2="Q_NO"/>
<map_variables variable_1="Q_sGC" variable_2="Q_sGC"/>
<map_variables variable_1="J_dif" variable_2="J_dif"/>
<map_variables variable_1="cGMP_EC" variable_2="cGMP_EC"/>
<map_variables variable_1="n_EC" variable_2="n_EC"/>
</connection>
<connection>
<map_components component_1="Phosphorylation_and_formation_of_eNOS_complexes" component_2="NO_sGC"/>
<map_variables variable_1="eNOS_CaM" variable_2="eNOS_CaM"/>
<map_variables variable_1="eNOS_CaM_star" variable_2="eNOS_CaM_star"/>
</connection>
<connection>
<map_components component_1="Activation_of_G_proteins" component_2="EC_par"/>
<map_variables variable_1="G" variable_2="G"/>
<map_variables variable_1="k_a" variable_2="k_a"/>
<map_variables variable_1="R_star" variable_2="R_star"/>
<map_variables variable_1="Gt" variable_2="Gt"/>
<map_variables variable_1="k_d" variable_2="k_d"/>
<map_variables variable_1="lambda" variable_2="lambda"/>
<map_variables variable_1="IP3" variable_2="IP3"/>
<map_variables variable_1="r_f" variable_2="r_f"/>
<map_variables variable_1="PIP2" variable_2="PIP2"/>
<map_variables variable_1="mu1" variable_2="mu1"/>
<map_variables variable_1="alpha" variable_2="alpha"/>
<map_variables variable_1="K_cp" variable_2="K_cp"/>
<map_variables variable_1="M_ATP" variable_2="M_ATP"/>
<map_variables variable_1="r_r" variable_2="r_r"/>
<map_variables variable_1="PIP2_t" variable_2="PIP2_t"/>
<map_variables variable_1="k_PIP2_positive" variable_2="k_PIP2_positive"/>
<map_variables variable_1="k_PIP2_negative" variable_2="k_PIP2_negative"/>
<map_variables variable_1="PIP3" variable_2="PIP3"/>
</connection>
<connection>
<map_components component_1="Calcium_signalling" component_2="EC_par"/>
<map_variables variable_1="Ca2_c" variable_2="Ca2_c"/>
<map_variables variable_1="Ca2_b" variable_2="Ca2_b"/>
<map_variables variable_1="Ca2_s" variable_2="Ca2_s"/>
<map_variables variable_1="q_rel" variable_2="q_rel"/>
<map_variables variable_1="q_res" variable_2="q_res"/>
<map_variables variable_1="q_out" variable_2="q_out"/>
<map_variables variable_1="q_in" variable_2="q_in"/>
<map_variables variable_1="k_leak" variable_2="k_leak"/>
<map_variables variable_1="v_r" variable_2="v_r"/>
<map_variables variable_1="k_rel" variable_2="k_rel"/>
<map_variables variable_1="k_2" variable_2="k_2"/>
<map_variables variable_1="k_res" variable_2="k_res"/>
<map_variables variable_1="k_3" variable_2="k_3"/>
<map_variables variable_1="k_out" variable_2="k_out"/>
<map_variables variable_1="k_5" variable_2="k_5"/>
<map_variables variable_1="q_MSIC" variable_2="q_MSIC"/>
<map_variables variable_1="q_CCE" variable_2="q_CCE"/>
<map_variables variable_1="q_max" variable_2="q_max"/>
<map_variables variable_1="N" variable_2="N"/>
<map_variables variable_1="W" variable_2="W"/>
<map_variables variable_1="Z" variable_2="Z"/>
<map_variables variable_1="W_0" variable_2="W_0"/>
<map_variables variable_1="k_CCE" variable_2="k_CCE"/>
<map_variables variable_1="Ca2_s0" variable_2="Ca2_s0"/>
<map_variables variable_1="Ca2_e" variable_2="Ca2_e"/>
<map_variables variable_1="psi" variable_2="psi"/>
<map_variables variable_1="xi" variable_2="xi"/>
<map_variables variable_1="k_on" variable_2="k_on"/>
<map_variables variable_1="k_off" variable_2="k_off"/>
<map_variables variable_1="B_tot" variable_2="B_tot"/>
</connection>
<connection>
<map_components component_1="Activation_of_protein_kinases" component_2="EC_par"/>
<map_variables variable_1="a_PI3K" variable_2="a_PI3K"/>
<map_variables variable_1="delta" variable_2="delta"/>
<map_variables variable_1="eta" variable_2="eta"/>
<map_variables variable_1="k_1p" variable_2="k_1p"/>
<map_variables variable_1="k_2p" variable_2="k_2p"/>
<map_variables variable_1="AKT_star" variable_2="AKT_star"/>
<map_variables variable_1="AKT_tot" variable_2="AKT_tot"/>
<map_variables variable_1="PKC_tot" variable_2="PKC_tot"/>
<map_variables variable_1="PKC_star" variable_2="PKC_star"/>
<map_variables variable_1="k_AKT_positive" variable_2="k_AKT_positive"/>
<map_variables variable_1="k_PKC_positive" variable_2="k_PKC_positive"/>
<map_variables variable_1="k_AKT_negative" variable_2="k_AKT_negative"/>
<map_variables variable_1="k_PKC_negative" variable_2="k_PKC_negative"/>
<map_variables variable_1="PIP3_min" variable_2="PIP3_min"/>
<map_variables variable_1="PIP3_max" variable_2="PIP3_max"/>
<map_variables variable_1="PIP2_tot" variable_2="PIP2_tot"/>
</connection>
<connection>
<map_components component_1="Phosphorylation_and_formation_of_eNOS_complexes" component_2="EC_par"/>
<map_variables variable_1="Ca4_CaM" variable_2="Ca4_CaM"/>
<map_variables variable_1="k_Ca4_CaM" variable_2="k_Ca4_CaM"/>
<map_variables variable_1="theta" variable_2="theta"/>
<map_variables variable_1="beta" variable_2="beta"/>
<map_variables variable_1="CaM_tot" variable_2="CaM_tot"/>
<map_variables variable_1="k_dCaM" variable_2="k_dCaM"/>
<map_variables variable_1="eNOS_CaM" variable_2="eNOS_CaM"/>
<map_variables variable_1="eNOS_CaM_star" variable_2="eNOS_CaM_star"/>
<map_variables variable_1="k_CaM_positive" variable_2="k_CaM_positive"/>
<map_variables variable_1="k_CaM_negative" variable_2="k_CaM_negative"/>
<map_variables variable_1="k_half_CaM" variable_2="k_half_CaM"/>
<map_variables variable_1="eNOS_Cav" variable_2="eNOS_Cav"/>
<map_variables variable_1="eNOS_tot" variable_2="eNOS_tot"/>
<map_variables variable_1="k_eAKT_positive" variable_2="k_eAKT_positive"/>
<map_variables variable_1="k_eAKT_negative" variable_2="k_eAKT_negative"/>
<map_variables variable_1="k_eAKT_max" variable_2="k_eAKT_max"/>
<map_variables variable_1="k_Thr_positive" variable_2="k_Thr_positive"/>
<map_variables variable_1="k_Thr_negative" variable_2="k_Thr_negative"/>
<map_variables variable_1="eNOS_Cav_0" variable_2="eNOS_Cav_0"/>
<map_variables variable_1="m_1" variable_2="m_1"/>
</connection>
<connection>
<map_components component_1="NO_production" component_2="EC_par"/>
<map_variables variable_1="NO_EC" variable_2="NO_EC"/>
<map_variables variable_1="Q_NO" variable_2="Q_NO"/>
<map_variables variable_1="O2" variable_2="O2"/>
<map_variables variable_1="k_mNO" variable_2="k_mNO"/>
<map_variables variable_1="eNOS_CaM" variable_2="eNOS_CaM"/>
<map_variables variable_1="eNOS_CaM_star" variable_2="eNOS_CaM_star"/>
<map_variables variable_1="Phi" variable_2="Phi"/>
<map_variables variable_1="Q_sGC" variable_2="Q_sGC"/>
<map_variables variable_1="sGC" variable_2="sGC"/>
<map_variables variable_1="R_NO_max" variable_2="R_NO_max"/>
<map_variables variable_1="a_0" variable_2="a_0"/>
<map_variables variable_1="a_1" variable_2="a_1"/>
<map_variables variable_1="cGMP_EC" variable_2="cGMP_EC"/>
<map_variables variable_1="v_cGMP_max" variable_2="v_cGMP_max"/>
<map_variables variable_1="g_0" variable_2="g_0"/>
<map_variables variable_1="g_1" variable_2="g_1"/>
<map_variables variable_1="X" variable_2="X"/>
<map_variables variable_1="k_cGMP" variable_2="k_cGMP"/>
<map_variables variable_1="r" variable_2="r"/>
<map_variables variable_1="b_0" variable_2="b_0"/>
<map_variables variable_1="b_1" variable_2="b_1"/>
<map_variables variable_1="All_NO" variable_2="All_NO"/>
<map_variables variable_1="NO_d" variable_2="NO_d"/>
<map_variables variable_1="lambda_NO" variable_2="lambda_NO"/>
</connection>
<connection>
<map_components component_1="kay2" component_2="Mp"/>
<map_variables variable_1="k3" variable_2="k3"/>
</connection>
<connection>
<map_components component_1="kay2" component_2="AMp"/>
<map_variables variable_1="k3" variable_2="k3"/>
</connection>
</model>
