Location: BG_GsProtein @ 3a1148e2a1e6 / BG_beta1AR.cellml

Author:
Shelley Fong <s.fong@auckland.ac.nz>
Date:
2021-07-07 17:53:54+12:00
Desc:
Comparing BG version against kinetic Saucerman03 model
Permanent Source URI:
https://models.physiomeproject.org/workspace/6f8/rawfile/3a1148e2a1e6d81f3921764f22b31f3a669ac390/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"/>
        <!-- kinetic parameters - for comparing. (basal reaction)-->
        <!--        var Km_basal_mM: mM {init: 1.03e0};
        var Km_basal: fmol_per_L {init: 1.03e12};
        var k1p_basal: per_sec_per_fmol_per_L {init: 1e-12};
        var k1m_basal: per_sec {init: 0.83};
        var k2p_basal: per_sec {init: 0.2};
        var k2m_basal: per_sec_per_fmol_per_L {init: 2.41e-13};
        var AC_tot: mM {init: 49.7e-6};
        var ATP_kinetic: mM {init: 0.00263157894736842};-->
        <!-- kinetic states-->
        <!--        var cAMP_kinetic: mM {init: 0.002631579};
        ode(cAMP_kinetic, t) = k2p_basal*AC_tot*ATP_kinetic/(Km_basal_mM+ATP_kinetic);-->
        <!-- Bond graph parameters, found using pinv of kinetic parameters-->
        <!-- 5jul21 with fastKineticConstant = 1e6 and NO constraints at eqlm-->
        <variable initial_value="7.59738e-06" name="kappa_B11" units="fmol_per_sec"/>
        <variable initial_value="3453.35" name="kappa_B12" units="fmol_per_sec"/>
        <variable initial_value="7.59738e-06" name="kappa_B21" units="fmol_per_sec"/>
        <variable initial_value="3453.35" name="kappa_B22" units="fmol_per_sec"/>
        <variable initial_value="5.60759e-11" name="kappa_P1" units="fmol_per_sec"/>
        <variable initial_value="1.55766e+07" name="kappa_P2" units="fmol_per_sec"/>
        <variable initial_value="0.544294" name="kappa_Act1" units="fmol_per_sec"/>
        <variable initial_value="0.544294" name="kappa_Act2" units="fmol_per_sec"/>
        <variable initial_value="68.4299" name="kappa_Hyd" units="fmol_per_sec"/>
        <variable initial_value="0.00837027" name="kappa_Reassoc" units="fmol_per_sec"/>
        <variable initial_value="29.3959" name="K_LR" units="per_fmol"/>
        <variable initial_value="0.0352751" name="K_B1d" units="per_fmol"/>
        <variable initial_value="8.20902e-09" name="K_BARK" units="per_fmol"/>
        <variable initial_value="289.574" name="K_LR_BARK" units="per_fmol"/>
        <variable initial_value="29.3959" name="K_LRG" units="per_fmol"/>
        <variable initial_value="289.574" name="K_LRG_BARK" units="per_fmol"/>
        <variable initial_value="2.88351e+09" name="K_B1p" units="per_fmol"/>
        <variable initial_value="4.71848e-12" name="K_B1tot" units="per_fmol"/>
        <variable initial_value="0.0136058" name="K_PKACI" units="per_fmol"/>
        <variable initial_value="0.0641987" name="K_PKACI_B1p" units="per_fmol"/>
        <variable initial_value="29.3959" name="K_RG" units="per_fmol"/>
        <variable initial_value="0.0116908" name="K_GaT" units="per_fmol"/>
        <variable initial_value="0.000157153" name="K_GBy" units="per_fmol"/>
        <variable initial_value="0.919864" name="K_GaD" units="per_fmol"/>
        <variable initial_value="1.44559e-10" name="K_GsGDP" units="per_fmol"/>
        <variable initial_value="1.58866e-08" name="K_Pi" units="per_fmol"/>
        <!-- States (and initial conditions)-->
        <!-- 7jul21 original concs from kinetic. Any zero concs  (e.g. complexes) = 1e-13 -->
        <variable initial_value="1.31E-05" name="q_LR" units="fmol"/>
        <variable initial_value="1e-13" name="q_B1d" units="fmol"/>
        <variable initial_value="0.0228" name="q_BARK" units="fmol"/>
        <variable initial_value="1e-13" name="q_LR_BARK" units="fmol"/>
        <variable initial_value="1e-13" name="q_LRG" units="fmol"/>
        <variable initial_value="1e-13" name="q_LRG_BARK" units="fmol"/>
        <variable initial_value="0.000043852" name="q_B1p" units="fmol"/>
        <variable initial_value="0.0004579" name="q_B1tot" units="fmol"/>
        <variable initial_value="0.002234014" name="q_PKACI" units="fmol"/>
        <variable initial_value="1e-13" name="q_PKACI_B1p" units="fmol"/>
        <variable initial_value="1e-13" name="q_RG" units="fmol"/>
        <!-- var q_RG: fmol {init: -3.75714E-05};
        var q_LRG: fmol {init: 0.000805744};-->
        <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="1e-13" name="q_GsGDP" units="fmol"/>
        <variable initial_value="1e-13" name="q_Pi" units="fmol"/>
        <!-- Bond variables-->
        <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_LR" 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" 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_RG" 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_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_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_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_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</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_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_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_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>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_LR</ci>
                </apply>
                <apply>
                    <minus/>
                    <ci>vB11</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>
                    <minus/>
                    <ci>vB21</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/>
                    <ci>vAct1</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) = B1AR_tot-->
        <variable initial_value="0.0004579" name="q_B1AR" units="fmol"/>
        <variable initial_value="0.00038" name="q_L" units="fmol"/>
        <variable name="c_B1AR" units="uM"/>
        <variable name="c_L" units="uM"/>
        <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>t</ci>
                    </bvar>
                    <ci>q_B1AR</ci>
                </apply>
                <apply>
                    <minus/>
                    <apply>
                        <minus/>
                        <apply>
                            <minus/>
                            <apply>
                                <diff/>
                                <bvar>
                                    <ci>t</ci>
                                </bvar>
                                <ci>q_B1tot</ci>
                            </apply>
                            <apply>
                                <diff/>
                                <bvar>
                                    <ci>t</ci>
                                </bvar>
                                <ci>q_RG</ci>
                            </apply>
                        </apply>
                        <apply>
                            <diff/>
                            <bvar>
                                <ci>t</ci>
                            </bvar>
                            <ci>q_LR</ci>
                        </apply>
                    </apply>
                    <apply>
                        <diff/>
                        <bvar>
                            <ci>t</ci>
                        </bvar>
                        <ci>q_LRG</ci>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>t</ci>
                    </bvar>
                    <ci>q_L</ci>
                </apply>
                <apply>
                    <minus/>
                    <apply>
                        <minus/>
                        <apply>
                            <diff/>
                            <bvar>
                                <ci>t</ci>
                            </bvar>
                            <ci>q_LR</ci>
                        </apply>
                    </apply>
                    <apply>
                        <diff/>
                        <bvar>
                            <ci>t</ci>
                        </bvar>
                        <ci>q_LRG</ci>
                    </apply>
                </apply>
            </apply>
            <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_B1AR</ci>
                <apply>
                    <divide/>
                    <apply>
                        <times/>
                        <cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
                        <ci>q_B1AR</ci>
                    </apply>
                    <ci>vol</ci>
                </apply>
            </apply>
        </math>
    </component>
</model>