- Author:
- Shelley Fong <s.fong@auckland.ac.nz>
- Date:
- 2021-09-02 10:56:13+12:00
- Desc:
- Fixing directionality in stoichiometric matrixc of Sig/LRGbinding module
- Permanent Source URI:
- https://models.cellml.org/workspace/6ba/rawfile/054ecf28ef47f90c026a8a0982035cbfce11b067/BG_beta1AR.cellml
<?xml version='1.0' encoding='UTF-8'?>
<!-- BG model of beta1 adrenergic receptor activation, based on saucerman2003
1jul21 initialising file
19 Jul beta1AR only: no Gactivation (see GsProtein)
1sept sig module is now an import - sharing vsig1-4 variables-->
<model name="BG_beta1AR" 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="per_sec" units_ref="per_sec"/>
<units name="J_per_K_per_mol" units_ref="J_per_K_per_mol"/>
<units name="C_per_mol" units_ref="C_per_mol"/>
<units name="fmol" units_ref="fmol"/>
<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="per_fmol" units_ref="per_fmol"/>
<units name="fmol_per_sec" units_ref="fmol_per_sec"/>
<units name="J_per_mol" units_ref="J_per_mol"/>
<units name="mM" units_ref="mM"/>
<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="../BG_LRGbinding/BG_LRGbinding.cellml">
<component component_ref="LRGbinding" name="LRGbinding"/>
<!-- comp LRGbinding_parameters using comp LRGbinding_parameters;-->
</import>
<component name="environment">
<variable name="time" public_interface="out" units="second"/>
<variable initial_value="0" name="q_LR_init" units="fmol"/>
<variable name="q_L_init" units="fmol"/>
<variable name="q_LR_global" public_interface="out" units="fmol"/>
<variable name="q_L_global" public_interface="out" units="fmol"/>
<variable name="del_q_LR" public_interface="in" units="fmol"/>
<variable name="del_q_L" public_interface="in" units="fmol"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>q_LR_global</ci>
<apply>
<plus/>
<ci>q_LR_init</ci>
<ci>del_q_LR</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>q_L_global</ci>
<apply>
<plus/>
<ci>q_L_init</ci>
<ci>del_q_L</ci>
</apply>
</apply>
<!-- stimulus-->
<apply>
<eq/>
<ci>q_L_init</ci>
<piecewise>
<piece>
<cn cellml:units="fmol" type="e-notation">1<sep/>0</cn>
<apply>
<lt/>
<ci>time</ci>
<cn cellml:units="second" type="e-notation">5<sep/>-2</cn>
</apply>
</piece>
<otherwise>
<cn cellml:units="fmol" type="e-notation">1<sep/>-3</cn>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<component name="B1AR_parameters">
<variable initial_value="5294.12" name="kappa_sig1" units="fmol_per_sec"/>
<variable initial_value="11.6347" name="kappa_sig2" units="fmol_per_sec"/>
<variable initial_value="2.53106" name="kappa_sig3" units="fmol_per_sec"/>
<variable initial_value="6192.68" name="kappa_sig4" units="fmol_per_sec"/>
<variable initial_value="5.61204e-05" name="kappa_B11" units="fmol_per_sec"/>
<variable initial_value="25509.3" name="kappa_B12" units="fmol_per_sec"/>
<variable initial_value="5.61204e-05" name="kappa_B21" units="fmol_per_sec"/>
<variable initial_value="25509.3" name="kappa_B22" units="fmol_per_sec"/>
<variable initial_value="0.0240723" name="kappa_P1" units="fmol_per_sec"/>
<variable initial_value="0.00231579" name="kappa_P2" units="fmol_per_sec"/>
<variable initial_value="0.400835" name="K_L" units="per_fmol"/>
<variable initial_value="0.340439" name="K_R" units="per_fmol"/>
<variable initial_value="0.468867" name="K_G" units="per_fmol"/>
<variable initial_value="712.082" name="K_LR" units="per_fmol"/>
<variable initial_value="181.201" name="K_RG" units="per_fmol"/>
<variable initial_value="712.082" name="K_LRG" units="per_fmol"/>
<variable initial_value="8.54499e-10" name="K_B1d" units="per_fmol"/>
<variable initial_value="3.8768e-05" name="K_BARK" units="per_fmol"/>
<variable initial_value="1.13958" name="K_LR_BARK" units="per_fmol"/>
<variable initial_value="1.13958" name="K_LRG_BARK" units="per_fmol"/>
<variable initial_value="0.0336751" name="K_B1p" units="per_fmol"/>
<variable initial_value="0.0336751" name="K_B1tot" units="per_fmol"/>
<variable initial_value="0.0390101" name="K_PKACI" units="per_fmol"/>
<variable initial_value="1.2076e-06" name="K_PKACI_B1p" units="per_fmol"/>
</component>
<component name="B1AR">
<variable name="time" public_interface="in" units="second"/>
<!-- Physical parameters-->
<variable name="R" public_interface="in" units="J_per_K_per_mol"/>
<variable name="T" public_interface="in" units="kelvin"/>
<!-- Bond graph parameters, found using pinv of kinetic parameters-->
<!-- var kappa_sig1: fmol_per_sec {pub: in};
var kappa_sig2: fmol_per_sec {pub: in};
var kappa_sig3: fmol_per_sec {pub: in};
var kappa_sig4: fmol_per_sec {pub: in};-->
<variable name="kappa_B11" public_interface="in" units="fmol_per_sec"/>
<variable name="kappa_B12" public_interface="in" units="fmol_per_sec"/>
<variable name="kappa_B21" public_interface="in" units="fmol_per_sec"/>
<variable name="kappa_B22" public_interface="in" units="fmol_per_sec"/>
<variable name="kappa_P1" public_interface="in" units="fmol_per_sec"/>
<variable name="kappa_P2" public_interface="in" units="fmol_per_sec"/>
<variable name="K_L" public_interface="in" units="per_fmol"/>
<variable name="K_R" public_interface="in" units="per_fmol"/>
<variable name="K_G" public_interface="in" units="per_fmol"/>
<variable name="K_LR" public_interface="in" units="per_fmol"/>
<variable name="K_RG" public_interface="in" units="per_fmol"/>
<variable name="K_LRG" public_interface="in" units="per_fmol"/>
<variable name="K_B1d" public_interface="in" units="per_fmol"/>
<variable name="K_BARK" public_interface="in" units="per_fmol"/>
<variable name="K_LR_BARK" public_interface="in" units="per_fmol"/>
<variable name="K_LRG_BARK" public_interface="in" units="per_fmol"/>
<variable name="K_B1p" public_interface="in" units="per_fmol"/>
<variable name="K_B1tot" public_interface="in" units="per_fmol"/>
<variable name="K_PKACI" public_interface="in" units="per_fmol"/>
<variable name="K_PKACI_B1p" public_interface="in" units="per_fmol"/>
<!-- States (and initial conditions)-->
<!-- 8jul21 original kinetic concs + equal division of enzyme states-->
<variable initial_value="0.0000508778" name="q_R" public_interface="out" units="fmol"/>
<variable initial_value="0.0290876489" name="q_G" public_interface="out" units="fmol"/>
<variable initial_value="0.0000508778" name="q_RG" public_interface="out" units="fmol"/>
<variable initial_value="0.0000508778" name="q_LRG" public_interface="out" units="fmol"/>
<variable initial_value="0.0000508778" name="q_LR_BARK" public_interface="out" units="fmol"/>
<variable initial_value="0.0000508778" name="q_LRG_BARK" public_interface="out" units="fmol"/>
<variable initial_value="0.0000508778" name="q_B1d" public_interface="out" units="fmol"/>
<variable initial_value="0.0000508778" name="q_B1p" public_interface="out" units="fmol"/>
<variable initial_value="0.008778" name="q_PKACI_B1p" public_interface="out" units="fmol"/>
<variable initial_value="0.0000508778" name="q_B1tot" public_interface="out" units="fmol"/>
<variable initial_value="0.00221209" name="q_PKACI" public_interface="out" units="fmol"/>
<variable initial_value="0.0228" name="q_BARK" public_interface="out" units="fmol"/>
<variable initial_value="0" name="q_L" public_interface="out" units="fmol"/>
<variable initial_value="0" name="q_LR" public_interface="out" units="fmol"/>
<variable name="q_L_global" public_interface="in" units="fmol"/>
<variable name="q_LR_global" public_interface="in" units="fmol"/>
<!-- Bond variables-->
<variable name="vsig1" public_interface="in" units="fmol_per_sec"/>
<variable name="vsig2" public_interface="in" units="fmol_per_sec"/>
<variable name="vsig3" public_interface="in" units="fmol_per_sec"/>
<variable name="vsig4" public_interface="in" units="fmol_per_sec"/>
<variable name="vB11" units="fmol_per_sec"/>
<variable name="vB12" units="fmol_per_sec"/>
<variable name="vB21" units="fmol_per_sec"/>
<variable name="vB22" units="fmol_per_sec"/>
<variable name="vP1" units="fmol_per_sec"/>
<variable name="vP2" units="fmol_per_sec"/>
<variable name="mu_L" units="J_per_mol"/>
<variable name="mu_R" units="J_per_mol"/>
<variable name="mu_G" units="J_per_mol"/>
<variable name="mu_LR" units="J_per_mol"/>
<variable name="mu_RG" units="J_per_mol"/>
<variable name="mu_LRG" units="J_per_mol"/>
<variable name="mu_B1d" units="J_per_mol"/>
<variable name="mu_BARK" units="J_per_mol"/>
<variable name="mu_LR_BARK" units="J_per_mol"/>
<variable name="mu_LRG_BARK" units="J_per_mol"/>
<variable name="mu_B1p" units="J_per_mol"/>
<variable name="mu_B1tot" units="J_per_mol"/>
<variable name="mu_PKACI" units="J_per_mol"/>
<variable name="mu_PKACI_B1p" units="J_per_mol"/>
<!-- Concentrations - for plotting-->
<variable name="c_L" public_interface="out" units="uM"/>
<variable name="c_R" public_interface="out" units="uM"/>
<variable name="c_G" public_interface="out" units="uM"/>
<variable name="c_LR" public_interface="out" units="uM"/>
<variable name="c_RG" public_interface="out" units="uM"/>
<variable name="c_B1d" public_interface="out" units="uM"/>
<variable name="c_BARK" public_interface="out" units="uM"/>
<variable name="c_LR_BARK" public_interface="out" units="uM"/>
<variable name="c_LRG" public_interface="out" units="uM"/>
<variable name="c_LRG_BARK" public_interface="out" units="uM"/>
<variable name="c_B1p" public_interface="out" units="uM"/>
<variable name="c_B1tot" public_interface="out" units="uM"/>
<variable name="c_PKACI" public_interface="out" units="uM"/>
<variable name="c_PKACI_B1p" public_interface="out" units="uM"/>
<variable initial_value="34.4" name="vol" units="pL"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>c_L</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<ci>q_L_global</ci>
</apply>
<ci>vol</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>c_R</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<ci>q_R</ci>
</apply>
<ci>vol</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>c_G</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<ci>q_G</ci>
</apply>
<ci>vol</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>c_LR</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<ci>q_LR_global</ci>
</apply>
<ci>vol</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>c_RG</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<ci>q_RG</ci>
</apply>
<ci>vol</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>c_B1d</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<ci>q_B1d</ci>
</apply>
<ci>vol</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>c_BARK</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<ci>q_BARK</ci>
</apply>
<ci>vol</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>c_LR_BARK</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<ci>q_LR_BARK</ci>
</apply>
<ci>vol</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>c_LRG</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<ci>q_LRG</ci>
</apply>
<ci>vol</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>c_LRG_BARK</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<ci>q_LRG_BARK</ci>
</apply>
<ci>vol</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>c_B1p</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<ci>q_B1p</ci>
</apply>
<ci>vol</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>c_B1tot</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<ci>q_B1tot</ci>
</apply>
<ci>vol</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>c_PKACI</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<ci>q_PKACI</ci>
</apply>
<ci>vol</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>c_PKACI_B1p</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<ci>q_PKACI_B1p</ci>
</apply>
<ci>vol</ci>
</apply>
</apply>
<!-- Constitutive equations-->
<apply>
<eq/>
<ci>mu_L</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
<apply>
<ln/>
<apply>
<times/>
<ci>K_L</ci>
<ci>q_L_global</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>mu_R</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
<apply>
<ln/>
<apply>
<times/>
<ci>K_R</ci>
<ci>q_R</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>mu_G</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
<apply>
<ln/>
<apply>
<times/>
<ci>K_G</ci>
<ci>q_G</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>mu_LR</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
<apply>
<ln/>
<apply>
<times/>
<ci>K_LR</ci>
<ci>q_LR_global</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>mu_RG</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
<apply>
<ln/>
<apply>
<times/>
<ci>K_RG</ci>
<ci>q_RG</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>mu_LRG</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
<apply>
<ln/>
<apply>
<times/>
<ci>K_LRG</ci>
<ci>q_LRG</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>mu_B1d</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
<apply>
<ln/>
<apply>
<times/>
<ci>K_B1d</ci>
<ci>q_B1d</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>mu_BARK</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
<apply>
<ln/>
<apply>
<times/>
<ci>K_BARK</ci>
<ci>q_BARK</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>mu_LR_BARK</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
<apply>
<ln/>
<apply>
<times/>
<ci>K_LR_BARK</ci>
<ci>q_LR_BARK</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>mu_LRG_BARK</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
<apply>
<ln/>
<apply>
<times/>
<ci>K_LRG_BARK</ci>
<ci>q_LRG_BARK</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>mu_B1p</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
<apply>
<ln/>
<apply>
<times/>
<ci>K_B1p</ci>
<ci>q_B1p</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>mu_B1tot</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
<apply>
<ln/>
<apply>
<times/>
<ci>K_B1tot</ci>
<ci>q_B1tot</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>mu_PKACI</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
<apply>
<ln/>
<apply>
<times/>
<ci>K_PKACI</ci>
<ci>q_PKACI</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>mu_PKACI_B1p</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
<apply>
<ln/>
<apply>
<times/>
<ci>K_PKACI_B1p</ci>
<ci>q_PKACI_B1p</ci>
</apply>
</apply>
</apply>
</apply>
<!-- vsig1 = kappa_sig1*exp((mu_R+mu_G)/(R*T))-exp(mu_RG/(R*T));
vsig2 = kappa_sig2*exp((mu_RG+mu_L)/(R*T))-exp(mu_LRG/(R*T));
vsig3 = kappa_sig3*exp((mu_LR+mu_G)/(R*T))-exp(mu_LRG/(R*T));
vsig4 = kappa_sig4*exp((mu_R+mu_L)/(R*T))-exp(mu_LR/(R*T));-->
<apply>
<eq/>
<ci>vB11</ci>
<apply>
<times/>
<ci>kappa_B11</ci>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>mu_LR</ci>
<ci>mu_BARK</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<ci>mu_LR_BARK</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>vB12</ci>
<apply>
<times/>
<ci>kappa_B12</ci>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<ci>mu_LR_BARK</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>mu_BARK</ci>
<ci>mu_B1d</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>vB21</ci>
<apply>
<times/>
<ci>kappa_B21</ci>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>mu_LRG</ci>
<ci>mu_BARK</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<ci>mu_LRG_BARK</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>vB22</ci>
<apply>
<times/>
<ci>kappa_B22</ci>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<ci>mu_LRG_BARK</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>mu_BARK</ci>
<ci>mu_B1d</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>vP1</ci>
<apply>
<times/>
<ci>kappa_P1</ci>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>mu_B1p</ci>
<ci>mu_PKACI</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<ci>mu_PKACI_B1p</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>vP2</ci>
<apply>
<times/>
<ci>kappa_P2</ci>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<ci>mu_PKACI_B1p</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>mu_PKACI</ci>
<ci>mu_B1tot</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
<variable name="v1b_kinetic" units="uM_per_sec"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>v1b_kinetic</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>vB12</ci>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
</apply>
<ci>vol</ci>
</apply>
</apply>
<!-- BG model-->
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>q_L</ci>
</apply>
<apply>
<minus/>
<apply>
<minus/>
<ci>vsig2</ci>
</apply>
<ci>vsig4</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>q_R</ci>
</apply>
<apply>
<minus/>
<apply>
<minus/>
<ci>vsig1</ci>
</apply>
<ci>vsig4</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>q_G</ci>
</apply>
<apply>
<minus/>
<apply>
<minus/>
<ci>vsig1</ci>
</apply>
<ci>vsig3</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>q_LR</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<minus/>
<ci>vB11</ci>
</apply>
<ci>vsig3</ci>
</apply>
<ci>vsig4</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>q_RG</ci>
</apply>
<apply>
<minus/>
<ci>vsig1</ci>
<ci>vsig2</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>q_B1d</ci>
</apply>
<apply>
<plus/>
<ci>vB12</ci>
<ci>vB22</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>q_BARK</ci>
</apply>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<plus/>
<ci>vB12</ci>
<ci>vB22</ci>
</apply>
<ci>vB11</ci>
</apply>
<ci>vB21</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>q_LR_BARK</ci>
</apply>
<apply>
<minus/>
<ci>vB11</ci>
<ci>vB12</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>q_LRG</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<ci>vB21</ci>
</apply>
<ci>vsig2</ci>
<ci>vsig3</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>q_LRG_BARK</ci>
</apply>
<apply>
<minus/>
<ci>vB21</ci>
<ci>vB22</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>q_B1p</ci>
</apply>
<apply>
<minus/>
<ci>vP1</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>q_B1tot</ci>
</apply>
<ci>vP2</ci>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>q_PKACI</ci>
</apply>
<apply>
<minus/>
<ci>vP2</ci>
<ci>vP1</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>q_PKACI_B1p</ci>
</apply>
<apply>
<minus/>
<ci>vP1</ci>
<ci>vP2</ci>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_1="environment" component_2="B1AR"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="del_q_LR" variable_2="q_LR"/>
<map_variables variable_1="del_q_L" variable_2="q_L"/>
<map_variables variable_1="q_LR_global" variable_2="q_LR_global"/>
<map_variables variable_1="q_L_global" variable_2="q_L_global"/>
</connection>
<connection>
<map_components component_1="B1AR_parameters" component_2="B1AR"/>
<map_variables variable_1="kappa_B11" variable_2="kappa_B11"/>
<map_variables variable_1="kappa_B12" variable_2="kappa_B12"/>
<map_variables variable_1="kappa_B21" variable_2="kappa_B21"/>
<map_variables variable_1="kappa_B22" variable_2="kappa_B22"/>
<map_variables variable_1="kappa_P1" variable_2="kappa_P1"/>
<map_variables variable_1="kappa_P2" variable_2="kappa_P2"/>
<map_variables variable_1="K_B1d" variable_2="K_B1d"/>
<map_variables variable_1="K_BARK" variable_2="K_BARK"/>
<map_variables variable_1="K_LR_BARK" variable_2="K_LR_BARK"/>
<map_variables variable_1="K_LRG_BARK" variable_2="K_LRG_BARK"/>
<map_variables variable_1="K_B1p" variable_2="K_B1p"/>
<map_variables variable_1="K_B1tot" variable_2="K_B1tot"/>
<map_variables variable_1="K_PKACI" variable_2="K_PKACI"/>
<map_variables variable_1="K_PKACI_B1p" variable_2="K_PKACI_B1p"/>
<map_variables variable_1="K_L" variable_2="K_L"/>
<map_variables variable_1="K_R" variable_2="K_R"/>
<map_variables variable_1="K_G" variable_2="K_G"/>
<map_variables variable_1="K_LR" variable_2="K_LR"/>
<map_variables variable_1="K_RG" variable_2="K_RG"/>
<map_variables variable_1="K_LRG" variable_2="K_LRG"/>
</connection>
<connection>
<map_components component_1="LRGbinding" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="B1AR_parameters" component_2="LRGbinding"/>
<map_variables variable_1="kappa_sig1" variable_2="kappa_sig1"/>
<map_variables variable_1="kappa_sig2" variable_2="kappa_sig2"/>
<map_variables variable_1="kappa_sig3" variable_2="kappa_sig3"/>
<map_variables variable_1="kappa_sig4" variable_2="kappa_sig4"/>
<map_variables variable_1="K_L" variable_2="K_L"/>
<map_variables variable_1="K_R" variable_2="K_R"/>
<map_variables variable_1="K_G" variable_2="K_G"/>
<map_variables variable_1="K_LR" variable_2="K_LR"/>
<map_variables variable_1="K_RG" variable_2="K_RG"/>
<map_variables variable_1="K_LRG" variable_2="K_LRG"/>
</connection>
<connection>
<map_components component_1="LRGbinding" component_2="B1AR"/>
<map_variables variable_1="vsig1" variable_2="vsig1"/>
<map_variables variable_1="vsig2" variable_2="vsig2"/>
<map_variables variable_1="vsig3" variable_2="vsig3"/>
<map_variables variable_1="vsig4" variable_2="vsig4"/>
<map_variables variable_1="q_L" variable_2="q_L"/>
<map_variables variable_1="q_LR" variable_2="q_LR"/>
<map_variables variable_1="q_LRG" variable_2="q_LRG"/>
<map_variables variable_1="q_R" variable_2="q_R"/>
<map_variables variable_1="q_RG" variable_2="q_RG"/>
<map_variables variable_1="q_G" variable_2="q_G"/>
</connection>
<connection>
<map_components component_1="constants" component_2="B1AR"/>
<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="LRGbinding"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
</connection>
</model>
