Location: semantic-annotation @ 92367a08b2bb / chang_fujita_1999.cellml

Author:

Dewan Sarwar <dsar941@UoA.auckland.ac.nz>

Date:

2020-06-25 21:17:52+12:00

Desc:

annotations changed for mackenzie model

Permanent Source URI:

https://staging.physiomeproject.org/workspace/267/rawfile/92367a08b2bb9612257ef3f32b6823adf5e0d53b/chang_fujita_1999.cellml

<?xml version='1.0' encoding='UTF-8'?>
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    <units name="millimolar">
        <unit exponent="-1.0" units="litre"/>
        <unit prefix="milli" units="mole"/>
    </units>
    <units name="flux">
        <unit exponent="-3.0" prefix="centi" units="metre"/>
        <unit exponent="-1.0" units="second"/>
        <unit prefix="milli" units="mole"/>
    </units>
    <units name="first_order_rate_constant">
        <unit exponent="-1.0" units="second"/>
    </units>
    <units name="second_order_rate_constant">
        <unit exponent="-1.0" units="second"/>
        <unit exponent="-1.0" units="millimolar"/>
    </units>
    <component name="environment">
        <variable cmeta:id="environment.time" name="time" public_interface="out" units="second"/>
    </component>
    <component cmeta:id="E" name="E">
        <variable cmeta:id="E.E" initial_value="0.08333" name="E" public_interface="out" units="millimolar"/>
        <variable cmeta:id="E.k23" name="k23" public_interface="in" units="second_order_rate_constant"/>
        <variable cmeta:id="E.k24" name="k24" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="E.k17" name="k17" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="E.k18" name="k18" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="E.k1" name="k1" public_interface="in" units="second_order_rate_constant"/>
        <variable cmeta:id="E.k2" name="k2" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="E.k3" name="k3" public_interface="in" units="second_order_rate_constant"/>
        <variable cmeta:id="E.k4" name="k4" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="E.ED" name="ED" public_interface="in" units="millimolar"/>
        <variable cmeta:id="E.E_" name="E_" public_interface="in" units="millimolar"/>
        <variable cmeta:id="E.ENa" name="ENa" public_interface="in" units="millimolar"/>
        <variable cmeta:id="E.ECl" name="ECl" public_interface="in" units="millimolar"/>
        <variable cmeta:id="E.D" name="D" public_interface="in" units="millimolar"/>
        <variable cmeta:id="E.Na" name="Na" public_interface="in" units="millimolar"/>
        <variable cmeta:id="E.Cl" name="Cl" public_interface="in" units="millimolar"/>
        <variable cmeta:id="E.time" name="time" public_interface="in" units="second"/>
        <math xmlns="http://www.w3.org/1998/Math/MathML">
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                <eq/>
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                    <diff/>
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                        <ci>time</ci>
                    </bvar>
                    <ci>E</ci>
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                    <minus/>
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                        <plus/>
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                            <times/>
                            <ci>k24</ci>
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                            <times/>
                            <ci>k18</ci>
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                            <times/>
                            <ci>k2</ci>
                            <ci>ENa</ci>
                        </apply>
                        <apply>
                            <times/>
                            <ci>k4</ci>
                            <ci>ECl</ci>
                        </apply>
                    </apply>
                    <apply>
                        <plus/>
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                            <times/>
                            <ci>k23</ci>
                            <ci>D</ci>
                            <ci>E</ci>
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                            <times/>
                            <ci>k17</ci>
                            <ci>E</ci>
                        </apply>
                        <apply>
                            <times/>
                            <ci>k1</ci>
                            <ci>Na</ci>
                            <ci>E</ci>
                        </apply>
                        <apply>
                            <times/>
                            <ci>k3</ci>
                            <ci>Cl</ci>
                            <ci>E</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
        </math>
    </component>
    <component cmeta:id="E_" name="E_">
        <variable cmeta:id="E_.E_" initial_value="0.08333" name="E_" public_interface="out" units="millimolar"/>
        <variable cmeta:id="E_.k29" name="k29" public_interface="in" units="second_order_rate_constant"/>
        <variable cmeta:id="E_.k30" name="k30" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="E_.k17" name="k17" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="E_.k18" name="k18" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="E_.k11" name="k11" public_interface="in" units="second_order_rate_constant"/>
        <variable cmeta:id="E_.k12" name="k12" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="E_.k9" name="k9" public_interface="in" units="second_order_rate_constant"/>
        <variable cmeta:id="E_.k10" name="k10" public_interface="in" units="first_order_rate_constant"/>
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        <variable cmeta:id="E_.E" name="E" public_interface="in" units="millimolar"/>
        <variable cmeta:id="E_.ENa_" name="ENa_" public_interface="in" units="millimolar"/>
        <variable cmeta:id="E_.ECl_" name="ECl_" public_interface="in" units="millimolar"/>
        <variable cmeta:id="E_.D_" name="D_" public_interface="in" units="millimolar"/>
        <variable cmeta:id="E_.Na_" name="Na_" public_interface="in" units="millimolar"/>
        <variable cmeta:id="E_.Cl_" name="Cl_" public_interface="in" units="millimolar"/>
        <variable cmeta:id="E_.time" name="time" public_interface="in" units="second"/>
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                    <diff/>
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                        <ci>time</ci>
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                            <times/>
                            <ci>k30</ci>
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                            <times/>
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                            <times/>
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                            <times/>
                            <ci>k12</ci>
                            <ci>ECl_</ci>
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                        <plus/>
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                            <times/>
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                            <times/>
                            <ci>k18</ci>
                            <ci>E_</ci>
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                        <apply>
                            <times/>
                            <ci>k9</ci>
                            <ci>Na_</ci>
                            <ci>E_</ci>
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                        <apply>
                            <times/>
                            <ci>k11</ci>
                            <ci>Cl_</ci>
                            <ci>E_</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
        </math>
    </component>
    <component cmeta:id="ED" name="ED">
        <variable cmeta:id="ED.ED" initial_value="0.08333" name="ED" public_interface="out" units="millimolar"/>
        <variable cmeta:id="ED.k23" name="k23" public_interface="in" units="second_order_rate_constant"/>
        <variable cmeta:id="ED.k24" name="k24" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="ED.k21" name="k21" public_interface="in" units="second_order_rate_constant"/>
        <variable cmeta:id="ED.k22" name="k22" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="ED.E" name="E" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ED.ENaD" name="ENaD" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ED.D" name="D" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ED.Na" name="Na" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ED.time" name="time" public_interface="in" units="second"/>
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                            <times/>
                            <ci>k23</ci>
                            <ci>E</ci>
                            <ci>D</ci>
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                            <times/>
                            <ci>k22</ci>
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                        <plus/>
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                            <times/>
                            <ci>k24</ci>
                            <ci>ED</ci>
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                        <apply>
                            <times/>
                            <ci>k21</ci>
                            <ci>Na</ci>
                            <ci>ED</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
        </math>
    </component>
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        <variable cmeta:id="ED_.k29" name="k29" public_interface="in" units="second_order_rate_constant"/>
        <variable cmeta:id="ED_.k30" name="k30" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="ED_.k27" name="k27" public_interface="in" units="second_order_rate_constant"/>
        <variable cmeta:id="ED_.k28" name="k28" public_interface="in" units="first_order_rate_constant"/>
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        <variable cmeta:id="ED_.Na_" name="Na_" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ED_.time" name="time" public_interface="in" units="second"/>
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                <eq/>
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                    <diff/>
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                        <ci>time</ci>
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                    <ci>ED_</ci>
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                    <minus/>
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                            <times/>
                            <ci>k29</ci>
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                            <times/>
                            <ci>k28</ci>
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                        <plus/>
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                            <times/>
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                            <times/>
                            <ci>k27</ci>
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                        </apply>
                    </apply>
                </apply>
            </apply>
        </math>
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        <variable cmeta:id="ENaD.k25" name="k25" public_interface="in" units="second_order_rate_constant"/>
        <variable cmeta:id="ENaD.k26" name="k26" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="ENaD.k21" name="k21" public_interface="in" units="second_order_rate_constant"/>
        <variable cmeta:id="ENaD.k22" name="k22" public_interface="in" units="first_order_rate_constant"/>
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        <variable cmeta:id="ENaD.ENa" name="ENa" public_interface="in" units="millimolar"/>
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        <variable cmeta:id="ENaD.time" name="time" public_interface="in" units="second"/>
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                        <ci>time</ci>
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                            <times/>
                            <ci>k21</ci>
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                            <times/>
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                            <times/>
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                            <times/>
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                            <ci>ENaD</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
        </math>
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        <variable cmeta:id="ENaD_.k28" name="k28" public_interface="in" units="first_order_rate_constant"/>
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                            <times/>
                            <ci>k27</ci>
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                            <times/>
                            <ci>k31</ci>
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                            <times/>
                            <ci>k28</ci>
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                            <ci>k32</ci>
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                    </apply>
                </apply>
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        <variable cmeta:id="ENa.D" name="D" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ENa.Na" name="Na" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ENa.Cl" name="Cl" public_interface="in" units="millimolar"/>
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                            <times/>
                            <ci>k7</ci>
                            <ci>Na</ci>
                            <ci>ECl</ci>
                        </apply>
                        <apply>
                            <times/>
                            <ci>k4</ci>
                            <ci>ECl</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
        </math>
    </component>
    <component cmeta:id="ECl_" name="ECl_">
        <variable cmeta:id="ECl_.ECl_" initial_value="0.08333" name="ECl_" public_interface="out" units="millimolar"/>
        <variable cmeta:id="ECl_.k11" name="k11" public_interface="in" units="second_order_rate_constant"/>
        <variable cmeta:id="ECl_.k12" name="k12" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="ECl_.k15" name="k15" public_interface="in" units="second_order_rate_constant"/>
        <variable cmeta:id="ECl_.k16" name="k16" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="ECl_.E_" name="E_" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ECl_.ENaCl_" name="ENaCl_" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ECl_.Na_" name="Na_" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ECl_.Cl_" name="Cl_" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ECl_.time" name="time" public_interface="in" units="second"/>
        <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>time</ci>
                    </bvar>
                    <ci>ECl_</ci>
                </apply>
                <apply>
                    <minus/>
                    <apply>
                        <plus/>
                        <apply>
                            <times/>
                            <ci>k11</ci>
                            <ci>Cl_</ci>
                            <ci>E_</ci>
                        </apply>
                        <apply>
                            <times/>
                            <ci>k16</ci>
                            <ci>ENaCl_</ci>
                        </apply>
                    </apply>
                    <apply>
                        <plus/>
                        <apply>
                            <times/>
                            <ci>k15</ci>
                            <ci>Na_</ci>
                            <ci>ECl_</ci>
                        </apply>
                        <apply>
                            <times/>
                            <ci>k12</ci>
                            <ci>ECl_</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
        </math>
    </component>
    <component cmeta:id="ENaCl" name="ENaCl">
        <variable cmeta:id="ENaCl.ENaCl" initial_value="0.08333" name="ENaCl" public_interface="out" units="millimolar"/>
        <variable cmeta:id="ENaCl.k7" name="k7" public_interface="in" units="second_order_rate_constant"/>
        <variable cmeta:id="ENaCl.k8" name="k8" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="ENaCl.k5" name="k5" public_interface="in" units="second_order_rate_constant"/>
        <variable cmeta:id="ENaCl.k6" name="k6" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="ENaCl.k19" name="k19" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="ENaCl.k20" name="k20" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="ENaCl.ENa" name="ENa" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ENaCl.ECl" name="ECl" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ENaCl.ENaCl_" name="ENaCl_" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ENaCl.Na" name="Na" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ENaCl.Cl" name="Cl" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ENaCl.time" name="time" public_interface="in" units="second"/>
        <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>time</ci>
                    </bvar>
                    <ci>ENaCl</ci>
                </apply>
                <apply>
                    <minus/>
                    <apply>
                        <plus/>
                        <apply>
                            <times/>
                            <ci>k5</ci>
                            <ci>Cl</ci>
                            <ci>ENa</ci>
                        </apply>
                        <apply>
                            <times/>
                            <ci>k7</ci>
                            <ci>Na</ci>
                            <ci>ECl</ci>
                        </apply>
                        <apply>
                            <times/>
                            <ci>k20</ci>
                            <ci>ENaCl_</ci>
                        </apply>
                    </apply>
                    <apply>
                        <plus/>
                        <apply>
                            <times/>
                            <ci>k6</ci>
                            <ci>ENaCl</ci>
                        </apply>
                        <apply>
                            <times/>
                            <ci>k8</ci>
                            <ci>ENaCl</ci>
                        </apply>
                        <apply>
                            <times/>
                            <ci>k19</ci>
                            <ci>ENaCl</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
        </math>
    </component>
    <component cmeta:id="ENaCl_" name="ENaCl_">
        <variable cmeta:id="ENaCl_.ENaCl_" initial_value="0.08333" name="ENaCl_" public_interface="out" units="millimolar"/>
        <variable cmeta:id="ENaCl_.k15" name="k15" public_interface="in" units="second_order_rate_constant"/>
        <variable cmeta:id="ENaCl_.k16" name="k16" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="ENaCl_.k13" name="k13" public_interface="in" units="second_order_rate_constant"/>
        <variable cmeta:id="ENaCl_.k14" name="k14" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="ENaCl_.k19" name="k19" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="ENaCl_.k20" name="k20" public_interface="in" units="first_order_rate_constant"/>
        <variable cmeta:id="ENaCl_.ENa_" name="ENa_" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ENaCl_.ECl_" name="ECl_" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ENaCl_.ENaCl" name="ENaCl" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ENaCl_.Na_" name="Na_" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ENaCl_.Cl_" name="Cl_" public_interface="in" units="millimolar"/>
        <variable cmeta:id="ENaCl_.time" name="time" public_interface="in" units="second"/>
        <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>time</ci>
                    </bvar>
                    <ci>ENaCl_</ci>
                </apply>
                <apply>
                    <minus/>
                    <apply>
                        <plus/>
                        <apply>
                            <times/>
                            <ci>k13</ci>
                            <ci>Cl_</ci>
                            <ci>ENa_</ci>
                        </apply>
                        <apply>
                            <times/>
                            <ci>k15</ci>
                            <ci>Na_</ci>
                            <ci>ECl_</ci>
                        </apply>
                        <apply>
                            <times/>
                            <ci>k19</ci>
                            <ci>ENaCl</ci>
                        </apply>
                    </apply>
                    <apply>
                        <plus/>
                        <apply>
                            <times/>
                            <ci>k14</ci>
                            <ci>ENaCl_</ci>
                        </apply>
                        <apply>
                            <times/>
                            <ci>k16</ci>
                            <ci>ENaCl_</ci>
                        </apply>
                        <apply>
                            <times/>
                            <ci>k20</ci>
                            <ci>ENaCl_</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
        </math>
    </component>
    <component name="reaction_constants">
        <variable cmeta:id="reaction_constants.k1" initial_value="1.0E5" name="k1" public_interface="out" units="second_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k2" initial_value="4.183E5" name="k2" public_interface="out" units="first_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k3" initial_value="1.0E5" name="k3" public_interface="out" units="second_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k4" initial_value="4.928E6" name="k4" public_interface="out" units="first_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k5" initial_value="1.0E5" name="k5" public_interface="out" units="second_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k6" initial_value="1.065E6" name="k6" public_interface="out" units="first_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k7" initial_value="1.0E5" name="k7" public_interface="out" units="second_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k8" initial_value="8.940E4" name="k8" public_interface="out" units="first_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k9" initial_value="1.0E5" name="k9" public_interface="out" units="second_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k10" initial_value="4.183E5" name="k10" public_interface="out" units="first_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k11" initial_value="1.0E5" name="k11" public_interface="out" units="second_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k12" initial_value="4.982E6" name="k12" public_interface="out" units="first_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k13" initial_value="1.0E5" name="k13" public_interface="out" units="second_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k14" initial_value="1.065E6" name="k14" public_interface="out" units="first_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k15" initial_value="1.0E5" name="k15" public_interface="out" units="second_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k16" initial_value="8.940E4" name="k16" public_interface="out" units="first_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k17" initial_value="4.587E5" name="k17" public_interface="out" units="first_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k18" initial_value="1.0E5" name="k18" public_interface="out" units="first_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k19" initial_value="1.0E3" name="k19" public_interface="out" units="first_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k20" initial_value="2.180E2" name="k20" public_interface="out" units="first_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k21" initial_value="1.0E5" name="k21" public_interface="out" units="second_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k22" initial_value="4.183E5" name="k22" public_interface="out" units="first_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k23" initial_value="1.0E5" name="k23" public_interface="out" units="second_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k24" initial_value="3.192E1" name="k24" public_interface="out" units="first_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k25" initial_value="1.0E5" name="k25" public_interface="out" units="second_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k26" initial_value="3.192E1" name="k26" public_interface="out" units="first_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k27" initial_value="1.0E5" name="k27" public_interface="out" units="second_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k28" initial_value="1.389E5" name="k28" public_interface="out" units="first_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k29" initial_value="1.0E5" name="k29" public_interface="out" units="second_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k30" initial_value="3.514E-1" name="k30" public_interface="out" units="first_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k31" initial_value="1.0E5" name="k31" public_interface="out" units="second_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.k32" initial_value="1.166E-1" name="k32" public_interface="out" units="first_order_rate_constant"/>
        <variable cmeta:id="reaction_constants.Na" initial_value="50.0" name="Na" public_interface="out" units="millimolar"/>
        <variable cmeta:id="reaction_constants.Cl" initial_value="96.0" name="Cl" public_interface="out" units="millimolar"/>
        <variable cmeta:id="reaction_constants.D" initial_value="1.0E-6" name="D" public_interface="out" units="millimolar"/>
        <variable cmeta:id="reaction_constants.Cl_" initial_value="40.0" name="Cl_" public_interface="out" units="millimolar"/>
        <variable cmeta:id="reaction_constants.Na_" initial_value="10.0" name="Na_" public_interface="out" units="millimolar"/>
        <variable cmeta:id="reaction_constants.D_" initial_value="1.0E-6" name="D_" public_interface="out" units="millimolar"/>
        <variable cmeta:id="reaction_constants.J_Na" name="J_Na" public_interface="out" units="flux"/>
        <variable cmeta:id="reaction_constants.ENa" name="ENa" public_interface="in" units="millimolar"/>
        <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
                <eq/>
                <ci>J_Na</ci>
                <apply>
                    <minus/>
                    <apply>
                        <times/>
                        <ci>k19</ci>
                        <ci>ENa</ci>
                        <ci>Cl</ci>
                    </apply>
                    <apply>
                        <times/>
                        <ci>k20</ci>
                        <ci>ENa</ci>
                        <ci>Cl_</ci>
                    </apply>
                </apply>
            </apply>
        </math>
    </component>
    <connection>
        <map_components component_1="reaction_constants" component_2="ECl_"/>
        <map_variables variable_1="k16" variable_2="k16"/>
        <map_variables variable_1="Cl_" variable_2="Cl_"/>
        <map_variables variable_1="k11" variable_2="k11"/>
        <map_variables variable_1="k12" variable_2="k12"/>
        <map_variables variable_1="Na_" variable_2="Na_"/>
        <map_variables variable_1="k15" variable_2="k15"/>
    </connection>
    <connection>
        <map_components component_1="ENaCl_" component_2="ENa_"/>
        <map_variables variable_1="ENaCl_" variable_2="ENaCl_"/>
    </connection>
    <connection>
        <map_components component_1="ENa" component_2="ENaCl"/>
        <map_variables variable_1="ENa" variable_2="ENa"/>
    </connection>
    <connection>
        <map_components component_1="ENaCl" component_2="ENaCl_"/>
        <map_variables variable_1="ENaCl" variable_2="ENaCl"/>
    </connection>
    <connection>
        <map_components component_1="ENaCl_" component_2="ECl_"/>
        <map_variables variable_1="ENaCl_" variable_2="ENaCl_"/>
    </connection>
    <connection>
        <map_components component_1="reaction_constants" component_2="ED"/>
        <map_variables variable_1="k22" variable_2="k22"/>
        <map_variables variable_1="k24" variable_2="k24"/>
        <map_variables variable_1="Na" variable_2="Na"/>
        <map_variables variable_1="k21" variable_2="k21"/>
        <map_variables variable_1="D" variable_2="D"/>
        <map_variables variable_1="k23" variable_2="k23"/>
    </connection>
    <connection>
        <map_components component_1="E_" component_2="ED_"/>
        <map_variables variable_1="E_" variable_2="E_"/>
    </connection>
    <connection>
        <map_components component_1="ENaD" component_2="ED"/>
        <map_variables variable_1="ENaD" variable_2="ENaD"/>
    </connection>
    <connection>
        <map_components component_1="reaction_constants" component_2="ECl"/>
        <map_variables variable_1="k4" variable_2="k4"/>
        <map_variables variable_1="k7" variable_2="k7"/>
        <map_variables variable_1="Na" variable_2="Na"/>
        <map_variables variable_1="k8" variable_2="k8"/>
        <map_variables variable_1="Cl" variable_2="Cl"/>
        <map_variables variable_1="k3" variable_2="k3"/>
    </connection>
    <connection>
        <map_components component_1="ENaD_" component_2="ENa_"/>
        <map_variables variable_1="ENaD_" variable_2="ENaD_"/>
    </connection>
    <connection>
        <map_components component_1="ENa_" component_2="E_"/>
        <map_variables variable_1="ENa_" variable_2="ENa_"/>
    </connection>
    <connection>
        <map_components component_1="ENaCl" component_2="ENa"/>
        <map_variables variable_1="ENaCl" variable_2="ENaCl"/>
    </connection>
    <connection>
        <map_components component_1="reaction_constants" component_2="ENaD_"/>
        <map_variables variable_1="Na_" variable_2="Na_"/>
        <map_variables variable_1="k32" variable_2="k32"/>
        <map_variables variable_1="k31" variable_2="k31"/>
        <map_variables variable_1="k27" variable_2="k27"/>
        <map_variables variable_1="k28" variable_2="k28"/>
        <map_variables variable_1="D_" variable_2="D_"/>
    </connection>
    <connection>
        <map_components component_1="environment" component_2="ENaD"/>
        <map_variables variable_1="time" variable_2="time"/>
    </connection>
    <connection>
        <map_components component_1="environment" component_2="ECl"/>
        <map_variables variable_1="time" variable_2="time"/>
    </connection>
    <connection>
        <map_components component_1="reaction_constants" component_2="ENa_"/>
        <map_variables variable_1="Cl_" variable_2="Cl_"/>
        <map_variables variable_1="k9" variable_2="k9"/>
        <map_variables variable_1="Na_" variable_2="Na_"/>
        <map_variables variable_1="k10" variable_2="k10"/>
        <map_variables variable_1="k32" variable_2="k32"/>
        <map_variables variable_1="k13" variable_2="k13"/>
        <map_variables variable_1="k31" variable_2="k31"/>
        <map_variables variable_1="k14" variable_2="k14"/>
        <map_variables variable_1="D_" variable_2="D_"/>
    </connection>
    <connection>
        <map_components component_1="environment" component_2="E"/>
        <map_variables variable_1="time" variable_2="time"/>
    </connection>
    <connection>
        <map_components component_1="reaction_constants" component_2="ED_"/>
        <map_variables variable_1="Na_" variable_2="Na_"/>
        <map_variables variable_1="k30" variable_2="k30"/>
        <map_variables variable_1="k29" variable_2="k29"/>
        <map_variables variable_1="k27" variable_2="k27"/>
        <map_variables variable_1="k28" variable_2="k28"/>
        <map_variables variable_1="D_" variable_2="D_"/>
    </connection>
    <connection>
        <map_components component_1="environment" component_2="ENa_"/>
        <map_variables variable_1="time" variable_2="time"/>
    </connection>
    <connection>
        <map_components component_1="ENaCl" component_2="ECl"/>
        <map_variables variable_1="ENaCl" variable_2="ENaCl"/>
    </connection>
    <connection>
        <map_components component_1="E" component_2="E_"/>
        <map_variables variable_1="E" variable_2="E"/>
    </connection>
    <connection>
        <map_components component_1="ENa" component_2="ENaD"/>
        <map_variables variable_1="ENa" variable_2="ENa"/>
    </connection>
    <connection>
        <map_components component_1="ECl" component_2="E"/>
        <map_variables variable_1="ECl" variable_2="ECl"/>
    </connection>
    <connection>
        <map_components component_1="E" component_2="ECl"/>
        <map_variables variable_1="E" variable_2="E"/>
    </connection>
    <connection>
        <map_components component_1="environment" component_2="ENaD_"/>
        <map_variables variable_1="time" variable_2="time"/>
    </connection>
    <connection>
        <map_components component_1="environment" component_2="ENa"/>
        <map_variables variable_1="time" variable_2="time"/>
    </connection>
    <connection>
        <map_components component_1="ED_" component_2="ENaD_"/>
        <map_variables variable_1="ED_" variable_2="ED_"/>
    </connection>
    <connection>
        <map_components component_1="ECl_" component_2="E_"/>
        <map_variables variable_1="ECl_" variable_2="ECl_"/>
    </connection>
    <connection>
        <map_components component_1="reaction_constants" component_2="ENa"/>
        <map_variables variable_1="k2" variable_2="k2"/>
        <map_variables variable_1="k1" variable_2="k1"/>
        <map_variables variable_1="k25" variable_2="k25"/>
        <map_variables variable_1="k6" variable_2="k6"/>
        <map_variables variable_1="Na" variable_2="Na"/>
        <map_variables variable_1="k26" variable_2="k26"/>
        <map_variables variable_1="Cl" variable_2="Cl"/>
        <map_variables variable_1="k5" variable_2="k5"/>
        <map_variables variable_1="D" variable_2="D"/>
        <map_variables variable_1="ENa" variable_2="ENa"/>
    </connection>
    <connection>
        <map_components component_1="ED" component_2="ENaD"/>
        <map_variables variable_1="ED" variable_2="ED"/>
    </connection>
    <connection>
        <map_components component_1="environment" component_2="E_"/>
        <map_variables variable_1="time" variable_2="time"/>
    </connection>
    <connection>
        <map_components component_1="ECl" component_2="ENaCl"/>
        <map_variables variable_1="ECl" variable_2="ECl"/>
    </connection>
    <connection>
        <map_components component_1="ENa_" component_2="ENaCl_"/>
        <map_variables variable_1="ENa_" variable_2="ENa_"/>
    </connection>
    <connection>
        <map_components component_1="environment" component_2="ED"/>
        <map_variables variable_1="time" variable_2="time"/>
    </connection>
    <connection>
        <map_components component_1="environment" component_2="ED_"/>
        <map_variables variable_1="time" variable_2="time"/>
    </connection>
    <connection>
        <map_components component_1="environment" component_2="ENaCl_"/>
        <map_variables variable_1="time" variable_2="time"/>
    </connection>
    <connection>
        <map_components component_1="E_" component_2="E"/>
        <map_variables variable_1="E_" variable_2="E_"/>
    </connection>
    <connection>
        <map_components component_1="ENaD_" component_2="ED_"/>
        <map_variables variable_1="ENaD_" variable_2="ENaD_"/>
    </connection>
    <connection>
        <map_components component_1="ECl_" component_2="ENaCl_"/>
        <map_variables variable_1="ECl_" variable_2="ECl_"/>
    </connection>
    <connection>
        <map_components component_1="ENa" component_2="E"/>
        <map_variables variable_1="ENa" variable_2="ENa"/>
    </connection>
    <connection>
        <map_components component_1="ENaCl_" component_2="ENaCl"/>
        <map_variables variable_1="ENaCl_" variable_2="ENaCl_"/>
    </connection>
    <connection>
        <map_components component_1="ED" component_2="E"/>
        <map_variables variable_1="ED" variable_2="ED"/>
    </connection>
    <connection>
        <map_components component_1="ENaD" component_2="ENa"/>
        <map_variables variable_1="ENaD" variable_2="ENaD"/>
    </connection>
    <connection>
        <map_components component_1="E_" component_2="ENa_"/>
        <map_variables variable_1="E_" variable_2="E_"/>
    </connection>
    <connection>
        <map_components component_1="ENa_" component_2="ENaD_"/>
        <map_variables variable_1="ENa_" variable_2="ENa_"/>
    </connection>
    <connection>
        <map_components component_1="reaction_constants" component_2="ENaCl"/>
        <map_variables variable_1="k20" variable_2="k20"/>
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                <title xmlns="http://cellml.org/tmp-documentation">A kinetic model of the thiazide-sensitive Na-Cl cotransporter</title>
                <author xmlns="http://cellml.org/tmp-documentation">
                    <firstname xmlns="http://cellml.org/tmp-documentation">Catherine</firstname>
                    <surname xmlns="http://cellml.org/tmp-documentation">Lloyd</surname>
                    <affiliation xmlns="http://cellml.org/tmp-documentation">
                        <shortaffil xmlns="http://cellml.org/tmp-documentation">Auckland Bioengineering Institute, The University of Auckland</shortaffil>
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                <title xmlns="http://cellml.org/tmp-documentation">Model Status</title>
                <para xmlns="http://cellml.org/tmp-documentation">This CellML model runs in OpenCell and COR.  The units have ben checked and they are consistent.  We are unsure whether or not the model recreates the published results as there are no simple figures of changing concentration against time.  Also sodium and chloride are set to constant values in this model - we suspect we need to derive an ODE equation based on the reaction figure (fig 1) in the paper.</para>
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                <title xmlns="http://cellml.org/tmp-documentation">Model Structure</title>
                <para xmlns="http://cellml.org/tmp-documentation">ABSTRACT: The aim of this study was to construct a numerical model of the thiazide-sensitive Na-Cl cotransporter (TSC) that can predict kinetics of thiazide binding and substrate transport of TSC. We hypothesized that the mechanisms underlying these kinetic properties can be approximated by a state diagram in which the transporter has two binding sites, one for sodium and another for chloride and thiazide. On the basis of the state diagram, a system of linear equations that should be satisfied in the steady state was postulated. Numerical solution of these equations yielded model prediction of kinetics of thiazide binding and substrate transport. Rate constants, which determine transitional rates between states, were systematically adjusted to minimize a penalty function that was devised to quantitatively estimate the difference between model predictions and experimental results. With the resultant rate constants, the model could simulate the following experimental results: 1) dissociation constant of thiazide in the absence of sodium and chloride; 2) inhibitory effect of chloride on thiazide binding; 3) stimulatory effect of sodium on thiazide binding; 4) combined effects of sodium and chloride on thiazide binding; 5) dependence of sodium influx on extracellular sodium and chloride; and 6) inhibition of sodium influx by extracellular thiazide. We conclude that known kinetic properties of TSC can be predicted by a model which is based on a state diagram.</para>
                <para xmlns="http://cellml.org/tmp-documentation">The original paper reference is cited below:</para>
                <para xmlns="http://cellml.org/tmp-documentation">&#xd;
          A kinetic model of the thiazide-sensitive Na-Cl cotransporter, Hangil Chang and Toshiro Fujita, 1999,&#xd;
          <emphasis xmlns="http://cellml.org/tmp-documentation">American Journal of Physiology</emphasis>&#xd;
          , 276, F952-F959.&#xd;
          <ulink xmlns="http://cellml.org/tmp-documentation" url="http://www.ncbi.nlm.nih.gov/pubmed/10362783">PubMed ID: 10362783</ulink>
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                            <objectinfo xmlns="http://cellml.org/tmp-documentation">
                                <title xmlns="http://cellml.org/tmp-documentation">diagram of the model</title>
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                    <caption xmlns="http://cellml.org/tmp-documentation">&#xd;
            State diagram for the thiazide-sensitive Na-Cl cotransporter (TSC).  Transporter (E) has binding sites for sodium (Na ) and chloride (Cl).  Thiazide diuretics (D) compete with chloride for the same binding site.&#xd;
            <emphasis xmlns="http://cellml.org/tmp-documentation">_i</emphasis>&#xd;
            is used to indicate which symbols belong to the intracellular side.&#xd;
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            <dcterms:description xmlns:dcterms="http://purl.org/dc/terms/">transitional rate of dissociation Na_ ion from state ENaCl_ to state ECl_ on the intracellular compartment</dcterms:description>
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            <dcterms:description xmlns:dcterms="http://purl.org/dc/terms/">transitional rate of binding Na_ ion from state E_ to state ENa_ on the intracellular compartment</dcterms:description>
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            <dcterms:description xmlns:dcterms="http://purl.org/dc/terms/">transitional rate from state E to state E_ on the luminal compartment to intracellular compartment through the cell membrane</dcterms:description>
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        <rdf:Description xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:about="#ED_.k27">
            <dcterms:description xmlns:dcterms="http://purl.org/dc/terms/">transitional rate of binding Na_ ion from state ED_ to state ENaD_ on the intracellular compartment</dcterms:description>
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            <dcterms:description xmlns:dcterms="http://purl.org/dc/terms/">transitional rate of binding Na_ ion from state E_ to state ENa_ on the intracellular compartment</dcterms:description>
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        <rdf:Description xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:about="#E_.k29">
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        <rdf:Description xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" isDescribedBy="10362783" keyword="TSC" modelName="chang_fujita_1999" rdf:about="#chang_fujita_1999">
            <semsim:unknown xmlns:semsim="http://www.bhi.washington.edu/SemSim#">dissociation constant</semsim:unknown>
            <semsim:unknown xmlns:semsim="http://www.bhi.washington.edu/SemSim#">Thiazide</semsim:unknown>
            <ro:located_in xmlns:ro="http://www.obofoundry.org/ro/ro.owl#" rdf:resource="http://purl.obolibrary.org/obo/FMA_17721" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"/>
            <ro:compartmentOf xmlns:ro="http://www.obofoundry.org/ro/ro.owl#" rdf:resource="http://purl.obolibrary.org/obo/FMA_74550" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"/>
            <dcterms:abstract xmlns:dcterms="http://purl.org/dc/terms/">The aim of this study was to construct a numerical model of the thiazide-sensitive Na-Cl cotransporter (TSC) that can predict kinetics of thiazide binding and substrate transport of TSC. We hypothesized that the mechanisms underlying these kinetic properties can be approximated by a state diagram in which the transporter has two binding sites, one for sodium and another for chloride and thiazide. On the basis of the state diagram, a system of linear equations that should be satisfied in the steady state was postulated. Numerical solution of these equations yielded model prediction of kinetics of thiazide binding and substrate transport. Rate constants, which determine transitional rates between states, were systematically adjusted to minimize a penalty function that was devised to quantitatively estimate the difference between model predictions and experimental results. With the resultant rate constants, the model could simulate the following experimental results: 1) dissociation constant of thiazide in the absence of sodium and chloride; 2) inhibitory effect of chloride on thiazide binding; 3) stimulatory effect of sodium on thiazide binding; 4) combined effects of sodium and chloride on thiazide binding; 5) dependence of sodium influx on extracellular sodium and chloride; and 6) inhibition of sodium influx by extracellular thiazide. We conclude that known kinetic properties of TSC can be predicted by a model which is based on a state diagram.</dcterms:abstract>
            <vCard:FN xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Toshiro Fujita</vCard:FN>
            <semsim:unknown xmlns:semsim="http://www.bhi.washington.edu/SemSim#">Toshiro Fujita</semsim:unknown>
            <vCard:FN xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Hangil Chang</vCard:FN>
            <dcterms:keyword xmlns:dcterms="http://purl.org/dc/terms/">dissociation constant</dcterms:keyword>
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            <dcterms:title xmlns:dcterms="http://purl.org/dc/terms/">A kinetic model of the thiazide-sensitive Na-Cl cotransporter</dcterms:title>
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            <dcterms:keyword xmlns:dcterms="http://purl.org/dc/terms/">Thiazide</dcterms:keyword>
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            <semsim:unknown xmlns:semsim="http://www.bhi.washington.edu/SemSim#">A kinetic model of the thiazide-sensitive Na-Cl cotransporter</semsim:unknown>
            <semsim:unknown xmlns:semsim="http://www.bhi.washington.edu/SemSim#">Hangil Chang</semsim:unknown>
            <semsim:unknown xmlns:semsim="http://www.bhi.washington.edu/SemSim#">The aim of this study was to construct a numerical model of the thiazide-sensitive Na-Cl cotransporter (TSC) that can predict kinetics of thiazide binding and substrate transport of TSC. We hypothesized that the mechanisms underlying these kinetic properties can be approximated by a state diagram in which the transporter has two binding sites, one for sodium and another for chloride and thiazide. On the basis of the state diagram, a system of linear equations that should be satisfied in the steady state was postulated. Numerical solution of these equations yielded model prediction of kinetics of thiazide binding and substrate transport. Rate constants, which determine transitional rates between states, were systematically adjusted to minimize a penalty function that was devised to quantitatively estimate the difference between model predictions and experimental results. With the resultant rate constants, the model could simulate the following experimental results: 1) dissociation constant of thiazide in the absence of sodium and chloride; 2) inhibitory effect of chloride on thiazide binding; 3) stimulatory effect of sodium on thiazide binding; 4) combined effects of sodium and chloride on thiazide binding; 5) dependence of sodium influx on extracellular sodium and chloride; and 6) inhibition of sodium influx by extracellular thiazide. We conclude that known kinetic properties of TSC can be predicted by a model which is based on a state diagram.</semsim:unknown>
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