- Author:
- Shelley Fong <s.fong@auckland.ac.nz>
- Date:
- 2021-07-08 17:36:05+12:00
- Desc:
- Adding scheme for making LRG from L,R,G
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/6f8/rawfile/810eac117f2e040ef6f0932bcbc09346888139ac/BG_beta1AR.cellml
<?xml version='1.0' encoding='UTF-8'?>
<!-- BG model of beta1 adrenergic receptor activation + Gs ctivation, based on saucerman2003, v1
1jul21 initialising file -->
<model name="BG_beta1AR" xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#">
<units name="per_sec">
<unit exponent="-1" units="second"/>
</units>
<units name="J_per_K_per_mol">
<unit units="joule"/>
<unit exponent="-1" units="kelvin"/>
<unit exponent="-1" units="mole"/>
</units>
<units name="C_per_mol">
<unit units="coulomb"/>
<unit exponent="-1" units="mole"/>
</units>
<units name="fmol">
<unit prefix="femto" units="mole"/>
</units>
<units name="fmol_per_L">
<unit prefix="femto" units="mole"/>
<unit exponent="-1" units="litre"/>
</units>
<units name="fmol_per_L_per_sec">
<unit units="fmol_per_L"/>
<unit exponent="-1" units="second"/>
</units>
<units name="per_sec_per_fmol_per_L">
<unit exponent="-1" units="second"/>
<unit exponent="-1" units="fmol_per_L"/>
</units>
<units name="per_fmol">
<unit exponent="-1" units="fmol"/>
</units>
<units name="fmol_per_sec">
<unit units="fmol"/>
<unit exponent="-1" units="second"/>
</units>
<units name="J_per_mol">
<unit units="joule"/>
<unit exponent="-1" units="mole"/>
</units>
<units name="mM">
<unit prefix="milli" units="mole"/>
<unit exponent="-1" units="litre"/>
</units>
<units name="uM">
<unit prefix="micro" units="mole"/>
<unit exponent="-1" units="litre"/>
</units>
<units name="mM_per_sec">
<unit units="mM"/>
<unit exponent="-1.0" units="second"/>
</units>
<units name="uM_per_sec">
<unit units="uM"/>
<unit exponent="-1.0" units="second"/>
</units>
<units name="pL">
<unit prefix="pico" units="litre"/>
</units>
<units name="m_to_u">
<unit prefix="micro" units="second"/>
<unit prefix="milli" units="second"/>
</units>
<component name="environment">
<variable initial_value="0" name="t" units="second"/>
<!-- Physical parameters-->
<variable initial_value="8.31" name="R" units="J_per_K_per_mol"/>
<variable initial_value="310" name="T" units="kelvin"/>
<variable initial_value="96485" name="F" units="C_per_mol"/>
<!-- Bond graph parameters, found using pinv of kinetic parameters-->
<!-- 5jul21 with fastKineticConstant = 1e6 and NO constraints at eqlm-->
<!-- var kappa_B11: fmol_per_sec {init: 7.59738e-06};
var kappa_B12: fmol_per_sec {init: 3453.35};
var kappa_B21: fmol_per_sec {init: 7.59738e-06};
var kappa_B22: fmol_per_sec {init: 3453.35};
var kappa_P1: fmol_per_sec {init: 5.60759e-11};
var kappa_P2: fmol_per_sec {init: 1.55766e+07};
var kappa_Act1: fmol_per_sec {init: 0.544294};
var kappa_Act2: fmol_per_sec {init: 0.544294};
var kappa_Hyd: fmol_per_sec {init: 68.4299};
var kappa_Reassoc: fmol_per_sec {init: 0.00837027};
var K_LR: per_fmol {init: 29.3959};
var K_B1d: per_fmol {init: 0.0352751};
var K_BARK: per_fmol {init: 8.20902e-09};
var K_LR_BARK: per_fmol {init: 289.574};
var K_LRG: per_fmol {init: 29.3959};
var K_LRG_BARK: per_fmol {init: 289.574};
var K_B1p: per_fmol {init: 2.88351e+09};
var K_B1tot: per_fmol {init: 4.71848e-12};
var K_PKACI: per_fmol {init: 0.0136058};
var K_PKACI_B1p: per_fmol {init: 0.0641987};
var K_RG: per_fmol {init: 29.3959};
var K_GaT: per_fmol {init: 0.0116908};
var K_GBy: per_fmol {init: 0.000157153};
var K_GaD: per_fmol {init: 0.919864};
var K_GsGDP: per_fmol {init: 1.44559e-10};
var K_Pi: per_fmol {init: 1.58866e-08};-->
<!-- 8jul21 with fastKineticConstant = 1e6 and NO constraints at eqlm-->
<variable initial_value="1431.68" name="kappa_Sig1" units="fmol_per_sec"/>
<variable initial_value="1.13225e-22" name="kappa_Sig2" units="fmol_per_sec"/>
<variable initial_value="152.225" name="kappa_Sig3" units="fmol_per_sec"/>
<variable initial_value="0.0691932" name="kappa_Sig4" units="fmol_per_sec"/>
<variable initial_value="6.23841e-19" name="kappa_B11" units="fmol_per_sec"/>
<variable initial_value="0.173289" name="kappa_B12" units="fmol_per_sec"/>
<variable initial_value="2.77263e+06" name="kappa_B21" units="fmol_per_sec"/>
<variable initial_value="2.77263e+06" name="kappa_B22" units="fmol_per_sec"/>
<variable initial_value="0.00174317" name="kappa_P1" units="fmol_per_sec"/>
<variable initial_value="0.00210923" name="kappa_P2" units="fmol_per_sec"/>
<variable initial_value="1.97201e+10" name="kappa_Act1" units="fmol_per_sec"/>
<variable initial_value="6.91932e+10" name="kappa_Act2" units="fmol_per_sec"/>
<variable initial_value="2.48727e+07" name="kappa_Hyd" units="fmol_per_sec"/>
<variable initial_value="1.49591e+07" name="kappa_Reassoc" units="fmol_per_sec"/>
<variable initial_value="9.405e+12" name="K_L" units="per_fmol"/>
<variable initial_value="9.3907e+14" name="K_R" units="per_fmol"/>
<variable initial_value="1.36364e-30" name="K_G" units="per_fmol"/>
<variable initial_value="8.83195e+15" name="K_LR" units="per_fmol"/>
<variable initial_value="1.53666e-06" name="K_RG" units="per_fmol"/>
<variable initial_value="1.44523e-05" name="K_LRG" units="per_fmol"/>
<variable initial_value="1.44523e-05" name="K_B1d" units="per_fmol"/>
<variable initial_value="0.399293" name="K_BARK" units="per_fmol"/>
<variable initial_value="5.7707e+06" name="K_LR_BARK" units="per_fmol"/>
<variable initial_value="3.60669e-13" name="K_LRG_BARK" units="per_fmol"/>
<variable initial_value="71605.6" name="K_B1p" units="per_fmol"/>
<variable initial_value="8.9507e-08" name="K_B1tot" units="per_fmol"/>
<variable initial_value="0.0064092" name="K_PKACI" units="per_fmol"/>
<variable initial_value="0.000573668" name="K_PKACI_B1p" units="per_fmol"/>
<variable initial_value="0.648463" name="K_GaT" units="per_fmol"/>
<variable initial_value="7.81999e-05" name="K_GBy" units="per_fmol"/>
<variable initial_value="2999.46" name="K_GaD" units="per_fmol"/>
<variable initial_value="0.066849" name="K_GsGDP" units="per_fmol"/>
<variable initial_value="1.3404e-05" name="K_Pi" units="per_fmol"/>
<!-- States (and initial conditions)-->
<!-- 7jul21 original concs from kinetic. Any zero concs (e.g. complexes) = 1e-13
var q_L: fmol {init: 1.31E-05};
var q_R: fmol {init: 1.31E-05};
var q_G: fmol {init: 1.31E-05};
var q_LR: fmol {init: 1.31E-05};
var q_B1d: fmol {init: 1e-13};
var q_BARK: fmol {init: 0.0228};
var q_LR_BARK: fmol {init: 1e-13};
var q_LRG: fmol {init: 1e-13};
var q_LRG_BARK: fmol {init: 1e-13};
var q_B1p: fmol {init: 0.000043852};
var q_B1tot: fmol {init: 0.0004579};
var q_PKACI: fmol {init: 0.002234014};
var q_PKACI_B1p: fmol {init: 1e-13};
var q_RG: fmol {init: 1e-13};
var q_GaT: fmol {init: 0.0009519};
var q_GBy: fmol {init: 0.00097622};
var q_GaD: fmol {init: 2.44948E-05};
var q_GsGDP: fmol {init: 1e-13};
var q_Pi: fmol {init: 1e-13};-->
<!-- 8jul21 original kinetic concs + equal division of enzyme states-->
<variable initial_value="0.000167285" name="q_L" units="fmol"/>
<variable initial_value="1.697e-06" name="q_LR" units="fmol"/>
<variable initial_value="0.00010466" name="q_LRG" units="fmol"/>
<variable initial_value="1.697e-06" name="q_LR_BARK" units="fmol"/>
<variable initial_value="0.00010466" name="q_LRG_BARK" units="fmol"/>
<variable initial_value="0.000219725" name="q_R" units="fmol"/>
<variable initial_value="2.54602e-05" name="q_RG" units="fmol"/>
<variable initial_value="0" name="q_B1d" units="fmol"/>
<variable initial_value="2.1926e-05" name="q_B1p" units="fmol"/>
<variable initial_value="2.1926e-05" name="q_PKACI_B1p" units="fmol"/>
<variable initial_value="0.0004579" name="q_B1tot" units="fmol"/>
<variable initial_value="0.00221209" name="q_PKACI" units="fmol"/>
<variable initial_value="0.0228" name="q_BARK" units="fmol"/>
<variable initial_value="0.145305" name="q_G" units="fmol"/>
<variable initial_value="0.0009519" name="q_GaT" units="fmol"/>
<variable initial_value="0.00097622" name="q_GBy" units="fmol"/>
<variable initial_value="2.44948e-05" name="q_GaD" units="fmol"/>
<variable initial_value="0" name="q_GsGDP" units="fmol"/>
<variable initial_value="570" name="q_Pi" units="fmol"/>
<!-- Bond variables-->
<variable name="vSig1" units="fmol_per_sec"/>
<variable name="vSig2" units="fmol_per_sec"/>
<variable name="vSig3" units="fmol_per_sec"/>
<variable name="vSig4" 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="vAct1" units="fmol_per_sec"/>
<variable name="vAct2" units="fmol_per_sec"/>
<variable name="vHyd" units="fmol_per_sec"/>
<variable name="vReassoc" 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"/>
<variable name="mu_GaT" units="J_per_mol"/>
<variable name="mu_GBy" units="J_per_mol"/>
<variable name="mu_GaD" units="J_per_mol"/>
<variable name="mu_GsGDP" units="J_per_mol"/>
<variable name="mu_Pi" units="J_per_mol"/>
<!-- Concentrations - for plotting-->
<variable name="c_L" units="uM"/>
<variable name="c_R" units="uM"/>
<variable name="c_G" units="uM"/>
<variable name="c_LR" units="uM"/>
<variable name="c_B1d" units="uM"/>
<variable name="c_BARK" units="uM"/>
<variable name="c_LR_BARK" units="uM"/>
<variable name="c_LRG" units="uM"/>
<variable name="c_LRG_BARK" units="uM"/>
<variable name="c_B1p" units="uM"/>
<variable name="c_B1tot" units="uM"/>
<variable name="c_PKACI" units="uM"/>
<variable name="c_PKACI_B1p" units="uM"/>
<variable name="c_RG" units="uM"/>
<variable name="c_GaT" units="uM"/>
<variable name="c_GBy" units="uM"/>
<variable name="c_GaD" units="uM"/>
<variable name="c_GsGDP" units="uM"/>
<variable name="c_Pi" units="uM"/>
<variable initial_value="38.0" 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</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</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>
<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_GaT</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<ci>q_GaT</ci>
</apply>
<ci>vol</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>c_GBy</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<ci>q_GBy</ci>
</apply>
<ci>vol</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>c_GaD</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<ci>q_GaD</ci>
</apply>
<ci>vol</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>c_GsGDP</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<ci>q_GsGDP</ci>
</apply>
<ci>vol</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>c_Pi</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
<ci>q_Pi</ci>
</apply>
<ci>vol</ci>
</apply>
</apply>
<!-- Constitutive equations
Choosing equal split of potentials after Re:act1 and Re:act2 ???-->
<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</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</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>
<apply>
<eq/>
<ci>mu_GaT</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
<apply>
<ln/>
<apply>
<times/>
<ci>K_GaT</ci>
<ci>q_GaT</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>mu_GBy</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
<apply>
<ln/>
<apply>
<times/>
<ci>K_GBy</ci>
<ci>q_GBy</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>mu_GaD</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
<apply>
<ln/>
<apply>
<times/>
<ci>K_GaD</ci>
<ci>q_GaD</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>mu_GsGDP</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
<apply>
<ln/>
<apply>
<times/>
<ci>K_GsGDP</ci>
<ci>q_GsGDP</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>mu_Pi</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
<apply>
<ln/>
<apply>
<times/>
<ci>K_Pi</ci>
<ci>q_Pi</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>vSig1</ci>
<apply>
<times/>
<ci>kappa_Sig1</ci>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>mu_R</ci>
<ci>mu_G</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<ci>mu_RG</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>vSig2</ci>
<apply>
<times/>
<ci>kappa_Sig2</ci>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>mu_L</ci>
<ci>mu_R</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<ci>mu_LR</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>vSig3</ci>
<apply>
<times/>
<ci>kappa_Sig3</ci>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>mu_LR</ci>
<ci>mu_G</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<ci>mu_LRG</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>vSig4</ci>
<apply>
<times/>
<ci>kappa_Sig4</ci>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>mu_L</ci>
<ci>mu_RG</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<ci>mu_LRG</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<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>
<apply>
<eq/>
<ci>vAct1</ci>
<apply>
<times/>
<ci>kappa_Act1</ci>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<ci>mu_RG</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>mu_GaT</ci>
<ci>mu_GBy</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>vAct2</ci>
<apply>
<times/>
<ci>kappa_Act2</ci>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<ci>mu_LRG</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>mu_GaT</ci>
<ci>mu_GBy</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>vHyd</ci>
<apply>
<times/>
<ci>kappa_Hyd</ci>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<ci>mu_GaT</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>mu_GaD</ci>
<ci>mu_Pi</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>vReassoc</ci>
<apply>
<times/>
<ci>kappa_Reassoc</ci>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>mu_GaD</ci>
<ci>mu_GBy</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<ci>mu_GsGDP</ci>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
<!-- velocity in uM_per_sec-->
<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>
<!-- saucerman: not all reactions are accounted for.-->
<!-- correct BG model-->
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</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>t</ci>
</bvar>
<ci>q_R</ci>
</apply>
<apply>
<minus/>
<apply>
<minus/>
<ci>vSig1</ci>
</apply>
<ci>vSig2</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</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>t</ci>
</bvar>
<ci>q_LR</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<ci>vB11</ci>
</apply>
<ci>vSig2</ci>
</apply>
<ci>vSig3</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_B1d</ci>
</apply>
<apply>
<plus/>
<ci>vB12</ci>
<ci>vB22</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</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>t</ci>
</bvar>
<ci>q_LR_BARK</ci>
</apply>
<apply>
<minus/>
<ci>vB11</ci>
<ci>vB12</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_LRG</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<ci>vB21</ci>
</apply>
<ci>vSig3</ci>
<ci>vSig4</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_LRG_BARK</ci>
</apply>
<apply>
<minus/>
<ci>vB21</ci>
<ci>vB22</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_B1p</ci>
</apply>
<apply>
<minus/>
<ci>vP1</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_B1tot</ci>
</apply>
<ci>vP2</ci>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_PKACI</ci>
</apply>
<apply>
<minus/>
<ci>vP2</ci>
<ci>vP1</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_PKACI_B1p</ci>
</apply>
<apply>
<minus/>
<ci>vP1</ci>
<ci>vP2</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_RG</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<ci>vAct1</ci>
</apply>
<ci>vSig1</ci>
</apply>
<ci>vSig4</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_GaT</ci>
</apply>
<apply>
<minus/>
<apply>
<minus/>
<ci>vAct1</ci>
<ci>vAct2</ci>
</apply>
<ci>vHyd</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_GBy</ci>
</apply>
<apply>
<minus/>
<apply>
<minus/>
<ci>vAct1</ci>
<ci>vAct2</ci>
</apply>
<ci>vReassoc</ci>
</apply>
</apply>
<!-- ode(q_GaT, t) = 0{fmol_per_sec};
ode(q_GBy, t) = 0{fmol_per_sec};-->
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_GaD</ci>
</apply>
<apply>
<minus/>
<ci>vHyd</ci>
<ci>vReassoc</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_GsGDP</ci>
</apply>
<ci>vReassoc</ci>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>t</ci>
</bvar>
<ci>q_Pi</ci>
</apply>
<ci>vHyd</ci>
</apply>
</math>
<!-- conservation of B1AR and L (through ODEs)
L(IC) = L_totmax if LR(IC) = LRG(IC) = 0
B1AR(IC) = R -->
<!-- var q_B1AR: fmol {init: 0.0004579};
var q_L: fmol {init: 0.00038};
var c_B1AR: uM;
var c_L: uM;-->
<!-- ode(q_B1AR, t) = ode(q_B1tot, t)-ode(q_RG, t)-ode(q_LR, t)-ode(q_LRG, t);
ode(q_L, t) = -ode(q_LR, t)-ode(q_LRG, t);
c_L = 1e3{m_to_u}*q_L/vol;
c_B1AR = 1e3{m_to_u}*q_B1AR/vol;-->
</component>
</model>