<?xml version='1.0' encoding='UTF-8'?>
<model name="FCU_guanylylCyclase" 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="units_and_constants/units_BG.cellml">
<units name="mM" units_ref="mM"/>
<units name="fmol" units_ref="fmol"/>
<units name="per_fmol" units_ref="per_fmol"/>
<units name="J_per_mol" units_ref="J_per_mol"/>
<units name="fmol_per_sec" units_ref="fmol_per_sec"/>
<units name="C_per_mol" units_ref="C_per_mol"/>
<units name="J_per_C" units_ref="J_per_C"/>
<units name="microm3" units_ref="microm3"/>
<units name="fF" units_ref="fF"/>
<units name="fC" units_ref="fC"/>
<units name="per_second" units_ref="per_second"/>
<units name="per_sec" units_ref="per_sec"/>
<units name="J_per_K_per_mol" units_ref="J_per_K_per_mol"/>
<units name="fmol_per_L" units_ref="fmol_per_L"/>
<units name="fmol_per_L_per_sec" units_ref="fmol_per_L_per_sec"/>
<units name="per_sec_per_fmol_per_L" units_ref="per_sec_per_fmol_per_L"/>
<units name="uM" units_ref="uM"/>
<units name="mM_per_sec" units_ref="mM_per_sec"/>
<units name="uM_per_sec" units_ref="uM_per_sec"/>
<units name="pL" units_ref="pL"/>
<units name="m_to_u" units_ref="m_to_u"/>
</import>
<import xlink:href="units_and_constants/constants_BG.cellml">
<component component_ref="constants" name="constants"/>
</import>
<import xlink:href="HaiMurphy/BG_HaiMurphy.cellml">
<component component_ref="HaiMurphy" name="HaiMurphy"/>
</import>
<import xlink:href="cGMP/BG_cGMP.cellml">
<component component_ref="cGMP" name="cGMP"/>
</import>
<import xlink:href="sGC/BG_sGC.cellml">
<component component_ref="sGC" name="sGC"/>
</import>
<component name="BG_parameters">
<variable initial_value="0.0628586" name="kappa_R_12" public_interface="out" units="fmol_per_sec"/>
<variable initial_value="10.3507" name="kappa_R_34" public_interface="out" units="fmol_per_sec"/>
<variable initial_value="1.13145" name="kappa_R_56" public_interface="out" units="fmol_per_sec"/>
<variable initial_value="0.031236" name="kappa_R_78" public_interface="out" units="fmol_per_sec"/>
<variable initial_value="192.663" name="kappa_R_1a_cGMP" public_interface="out" units="fmol_per_sec"/>
<variable initial_value="0.00328297" name="kappa_R_1b_cGMP" public_interface="out" units="fmol_per_sec"/>
<variable initial_value="56591.2" name="kappa_R_2a_cGMP" public_interface="out" units="fmol_per_sec"/>
<variable initial_value="0.0110353" name="kappa_R_2b_cGMP" public_interface="out" units="fmol_per_sec"/>
<variable initial_value="3.61127e+06" name="kappa_R_1_sGC" public_interface="out" units="fmol_per_sec"/>
<variable initial_value="0.00328297" name="kappa_R_2_sGC" public_interface="out" units="fmol_per_sec"/>
<variable initial_value="4.92446" name="kappa_R_3_sGC" public_interface="out" units="fmol_per_sec"/>
<variable initial_value="0.0361127" name="kappa_R_4_sGC" public_interface="out" units="fmol_per_sec"/>
<variable initial_value="0.01" name="kappa_R_DNO_sGC" public_interface="out" units="fmol_per_sec"/>
<variable initial_value="1.65213" name="K_A" public_interface="out" units="per_fmol"/>
<variable initial_value="15.6959" name="K_M" public_interface="out" units="per_fmol"/>
<variable initial_value="0.105259" name="K_Mp" public_interface="out" units="per_fmol"/>
<variable initial_value="1.44065" name="K_AM" public_interface="out" units="per_fmol"/>
<variable initial_value="0.00966114" name="K_AMp" public_interface="out" units="per_fmol"/>
<variable initial_value="723.915" name="K_Pi" public_interface="out" units="per_fmol"/>
<variable initial_value="1" name="K_Ca_i" public_interface="out" units="per_fmol"/>
<variable initial_value="1" name="K_cGMP" public_interface="out" units="per_fmol"/>
<variable initial_value="17040" name="K_GTP" public_interface="out" units="per_fmol"/>
<variable initial_value="0.304602" name="K_E5c" public_interface="out" units="per_fmol"/>
<variable initial_value="17.6706" name="K_PDE" public_interface="out" units="per_fmol"/>
<variable initial_value="5190.42" name="K_GTP_E5c" public_interface="out" units="per_fmol"/>
<variable initial_value="35.3412" name="K_cGMP_PDE" public_interface="out" units="per_fmol"/>
<variable initial_value="0.0051282" name="K_GMP" public_interface="out" units="per_fmol"/>
<variable initial_value="0.0276911" name="K_Eb" public_interface="out" units="per_fmol"/>
<variable initial_value="1" name="K_NO" public_interface="out" units="per_fmol"/>
<variable initial_value="30.4602" name="K_E6c" public_interface="out" units="per_fmol"/>
<variable initial_value="0.1" name="K_NO_product" public_interface="out" units="per_fmol"/>
</component>
<component name="environment">
<variable name="t" public_interface="out" units="second"/>
<variable initial_value="1" name="vol_myo" public_interface="out" units="pL"/>
<!-- concentrations and molar amounts of GC, PDE, GMP, AM/M (etc) need to be sourced - they are currently guesses.-->
<variable initial_value="1e-6" name="q_A" public_interface="out" units="fmol"/>
<variable initial_value="1e-6" name="q_M" public_interface="out" units="fmol"/>
<variable initial_value="0" name="q_Mp" public_interface="out" units="fmol"/>
<variable initial_value="0" name="q_AM" public_interface="out" units="fmol"/>
<variable initial_value="0" name="q_AMp" public_interface="out" units="fmol"/>
<variable initial_value="15" name="q_Pi" public_interface="out" units="fmol"/>
<variable initial_value="1e-3" name="q_Ca_i" public_interface="out" units="fmol"/>
<variable initial_value="1e-6" name="q_cGMP" public_interface="out" units="fmol"/>
<variable initial_value="0.0005" name="q_GTP" public_interface="out" units="fmol"/>
<variable initial_value="1e-16" name="q_E5c" public_interface="out" units="fmol"/>
<variable initial_value="1e-10" name="q_PDE" public_interface="out" units="fmol"/>
<variable initial_value="1e-16" name="q_GTP_E5c" public_interface="out" units="fmol"/>
<variable initial_value="1e-16" name="q_cGMP_PDE" public_interface="out" units="fmol"/>
<variable initial_value="1e-16" name="q_GMP" public_interface="out" units="fmol"/>
<variable initial_value="1e-6" name="q_Eb" public_interface="out" units="fmol"/>
<variable initial_value="0.00836" name="q_NO" public_interface="out" units="fmol"/>
<variable initial_value="1e-16" name="q_E6c" public_interface="out" units="fmol"/>
<variable initial_value="1e-16" name="q_NO_product" public_interface="out" units="fmol"/>
<!-- HaiMurphy imports-->
<variable name="v_R_12" public_interface="in" units="fmol_per_sec"/>
<variable name="v_R_34" public_interface="in" units="fmol_per_sec"/>
<variable name="v_R_56" public_interface="in" units="fmol_per_sec"/>
<variable name="v_R_78" public_interface="in" units="fmol_per_sec"/>
<variable initial_value="1.66" name="n_Cai_SM" public_interface="out" units="dimensionless"/>
<!-- cGMP imports-->
<variable name="v_R_1a_cGMP" public_interface="in" units="fmol_per_sec"/>
<variable name="v_R_1b_cGMP" public_interface="in" units="fmol_per_sec"/>
<variable name="v_R_2a_cGMP" public_interface="in" units="fmol_per_sec"/>
<variable name="v_R_2b_cGMP" public_interface="in" units="fmol_per_sec"/>
<!-- sGC imports-->
<variable name="v_R_1_sGC" public_interface="in" units="fmol_per_sec"/>
<variable name="v_R_2_sGC" public_interface="in" units="fmol_per_sec"/>
<variable name="v_R_3_sGC" public_interface="in" units="fmol_per_sec"/>
<variable name="v_R_4_sGC" public_interface="in" units="fmol_per_sec"/>
<variable name="v_R_DNO_sGC" public_interface="in" units="fmol_per_sec"/>
<!-- constant rate of NO generation, converted from kinetic model J_NO-->
<variable initial_value="0.000114" name="v_NO_generation" units="fmol_per_sec"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_A</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<ci>v_R_34</ci>
</apply>
<ci>v_R_78</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_M</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<ci>v_R_12</ci>
</apply>
<ci>v_R_78</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_Mp</ci>
</apply>
<apply>
<minus/>
<ci>v_R_12</ci>
<ci>v_R_34</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_AM</ci>
</apply>
<apply>
<minus/>
<ci>v_R_56</ci>
<ci>v_R_78</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_AMp</ci>
</apply>
<apply>
<minus/>
<ci>v_R_34</ci>
<ci>v_R_56</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_Pi</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<ci>v_R_12</ci>
</apply>
<ci>v_R_56</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_Ca_i</ci>
</apply>
<apply>
<times/>
<ci>n_Cai_SM</ci>
<apply>
<minus/>
<apply>
<minus/>
<ci>v_R_12</ci>
</apply>
<ci>v_R_56</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_cGMP</ci>
</apply>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<plus/>
<ci>v_R_12</ci>
<ci>v_R_56</ci>
<ci>v_R_1b_cGMP</ci>
</apply>
<ci>v_R_2a_cGMP</ci>
</apply>
<ci>v_R_2b_cGMP</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>v_R_4_sGC</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_GTP</ci>
</apply>
<apply>
<minus/>
<ci>v_R_1a_cGMP</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_E5c</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<ci>v_R_1a_cGMP</ci>
</apply>
<ci>v_R_1b_cGMP</ci>
<ci>v_R_2_sGC</ci>
<ci>v_R_3_sGC</ci>
</apply>
<ci>v_R_4_sGC</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_PDE</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<ci>v_R_2a_cGMP</ci>
</apply>
<ci>v_R_2b_cGMP</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_GTP_E5c</ci>
</apply>
<apply>
<minus/>
<ci>v_R_1a_cGMP</ci>
<ci>v_R_1b_cGMP</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_cGMP_PDE</ci>
</apply>
<apply>
<minus/>
<ci>v_R_2a_cGMP</ci>
<ci>v_R_2b_cGMP</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_GMP</ci>
</apply>
<ci>v_R_2b_cGMP</ci>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_Eb</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<ci>v_R_1_sGC</ci>
</apply>
<ci>v_R_4_sGC</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_NO</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<ci>v_R_1_sGC</ci>
</apply>
<ci>v_R_4_sGC</ci>
</apply>
<ci>v_R_DNO_sGC</ci>
</apply>
<ci>v_NO_generation</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_E6c</ci>
</apply>
<apply>
<minus/>
<apply>
<minus/>
<ci>v_R_1_sGC</ci>
<ci>v_R_2_sGC</ci>
</apply>
<ci>v_R_3_sGC</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_NO_product</ci>
</apply>
<ci>v_R_DNO_sGC</ci>
</apply>
</math>
<!-- stress calculation: from original HM
stress = AM + AMp -->
<variable name="stress" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>stress</ci>
<apply>
<divide/>
<apply>
<plus/>
<ci>q_AM</ci>
<ci>q_AMp</ci>
</apply>
<cn cellml:units="fmol">1</cn>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_1="environment" component_2="HaiMurphy"/>
<map_variables variable_1="t" variable_2="time"/>
<map_variables variable_1="q_A" variable_2="q_A"/>
<map_variables variable_1="q_M" variable_2="q_M"/>
<map_variables variable_1="q_Mp" variable_2="q_Mp"/>
<map_variables variable_1="q_AM" variable_2="q_AM"/>
<map_variables variable_1="q_AMp" variable_2="q_AMp"/>
<map_variables variable_1="q_Pi" variable_2="q_Pi"/>
<map_variables variable_1="q_Ca_i" variable_2="q_Ca_i"/>
<map_variables variable_1="q_cGMP" variable_2="q_cGMP"/>
<map_variables variable_1="v_R_12" variable_2="v_R_12"/>
<map_variables variable_1="v_R_34" variable_2="v_R_34"/>
<map_variables variable_1="v_R_56" variable_2="v_R_56"/>
<map_variables variable_1="v_R_78" variable_2="v_R_78"/>
<map_variables variable_1="n_Cai_SM" variable_2="n_Cai_SM"/>
</connection>
<connection>
<map_components component_1="environment" component_2="cGMP"/>
<map_variables variable_1="t" variable_2="time"/>
<map_variables variable_1="q_GTP" variable_2="q_GTP"/>
<map_variables variable_1="q_E5c" variable_2="q_E5c"/>
<map_variables variable_1="q_cGMP" variable_2="q_cGMP"/>
<map_variables variable_1="q_PDE" variable_2="q_PDE"/>
<map_variables variable_1="q_GTP_E5c" variable_2="q_GTP_E5c"/>
<map_variables variable_1="q_cGMP_PDE" variable_2="q_cGMP_PDE"/>
<map_variables variable_1="q_GMP" variable_2="q_GMP"/>
<map_variables variable_1="v_R_1a_cGMP" variable_2="v_R_1a_cGMP"/>
<map_variables variable_1="v_R_1b_cGMP" variable_2="v_R_1b_cGMP"/>
<map_variables variable_1="v_R_2a_cGMP" variable_2="v_R_2a_cGMP"/>
<map_variables variable_1="v_R_2b_cGMP" variable_2="v_R_2b_cGMP"/>
</connection>
<connection>
<map_components component_1="environment" component_2="sGC"/>
<map_variables variable_1="t" variable_2="time"/>
<map_variables variable_1="q_Eb" variable_2="q_Eb"/>
<map_variables variable_1="q_NO" variable_2="q_NO"/>
<map_variables variable_1="q_E6c" variable_2="q_E6c"/>
<map_variables variable_1="q_E5c" variable_2="q_E5c"/>
<map_variables variable_1="q_cGMP" variable_2="q_cGMP"/>
<map_variables variable_1="q_NO_product" variable_2="q_NO_product"/>
<map_variables variable_1="v_R_1_sGC" variable_2="v_R_1_sGC"/>
<map_variables variable_1="v_R_2_sGC" variable_2="v_R_2_sGC"/>
<map_variables variable_1="v_R_3_sGC" variable_2="v_R_3_sGC"/>
<map_variables variable_1="v_R_4_sGC" variable_2="v_R_4_sGC"/>
<map_variables variable_1="v_R_DNO_sGC" variable_2="v_R_DNO_sGC"/>
</connection>
<connection>
<map_components component_1="BG_parameters" component_2="HaiMurphy"/>
<map_variables variable_1="kappa_R_12" variable_2="kappa_R_12"/>
<map_variables variable_1="kappa_R_34" variable_2="kappa_R_34"/>
<map_variables variable_1="kappa_R_56" variable_2="kappa_R_56"/>
<map_variables variable_1="kappa_R_78" variable_2="kappa_R_78"/>
<map_variables variable_1="K_A" variable_2="K_A"/>
<map_variables variable_1="K_M" variable_2="K_M"/>
<map_variables variable_1="K_Mp" variable_2="K_Mp"/>
<map_variables variable_1="K_AM" variable_2="K_AM"/>
<map_variables variable_1="K_AMp" variable_2="K_AMp"/>
<map_variables variable_1="K_Pi" variable_2="K_Pi"/>
<map_variables variable_1="K_Ca_i" variable_2="K_Ca_i"/>
<map_variables variable_1="K_cGMP" variable_2="K_cGMP"/>
</connection>
<connection>
<map_components component_1="BG_parameters" component_2="cGMP"/>
<map_variables variable_1="kappa_R_1a_cGMP" variable_2="kappa_R_1a_cGMP"/>
<map_variables variable_1="kappa_R_1b_cGMP" variable_2="kappa_R_1b_cGMP"/>
<map_variables variable_1="kappa_R_2a_cGMP" variable_2="kappa_R_2a_cGMP"/>
<map_variables variable_1="kappa_R_2b_cGMP" variable_2="kappa_R_2b_cGMP"/>
<map_variables variable_1="K_GTP" variable_2="K_GTP"/>
<map_variables variable_1="K_E5c" variable_2="K_E5c"/>
<map_variables variable_1="K_cGMP" variable_2="K_cGMP"/>
<map_variables variable_1="K_PDE" variable_2="K_PDE"/>
<map_variables variable_1="K_GTP_E5c" variable_2="K_GTP_E5c"/>
<map_variables variable_1="K_cGMP_PDE" variable_2="K_cGMP_PDE"/>
<map_variables variable_1="K_GMP" variable_2="K_GMP"/>
</connection>
<connection>
<map_components component_1="BG_parameters" component_2="sGC"/>
<map_variables variable_1="kappa_R_1_sGC" variable_2="kappa_R_1_sGC"/>
<map_variables variable_1="kappa_R_2_sGC" variable_2="kappa_R_2_sGC"/>
<map_variables variable_1="kappa_R_3_sGC" variable_2="kappa_R_3_sGC"/>
<map_variables variable_1="kappa_R_4_sGC" variable_2="kappa_R_4_sGC"/>
<map_variables variable_1="kappa_R_DNO_sGC" variable_2="kappa_R_DNO_sGC"/>
<map_variables variable_1="K_Eb" variable_2="K_Eb"/>
<map_variables variable_1="K_NO" variable_2="K_NO"/>
<map_variables variable_1="K_E6c" variable_2="K_E6c"/>
<map_variables variable_1="K_E5c" variable_2="K_E5c"/>
<map_variables variable_1="K_cGMP" variable_2="K_cGMP"/>
<map_variables variable_1="K_NO_product" variable_2="K_NO_product"/>
</connection>
<connection>
<map_components component_1="constants" component_2="HaiMurphy"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
</connection>
<connection>
<map_components component_1="constants" component_2="cGMP"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
</connection>
<connection>
<map_components component_1="constants" component_2="sGC"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
</connection>
</model>
