- Author:
- AnandR <a.rampadarath@auckland.ac.nz>
- Date:
- 2019-03-01 15:11:41+13:00
- Desc:
- Annotated cellml model using semgen
- Permanent Source URI:
- https://models.cellml.org/workspace/570/rawfile/4051e717230ddb33d9a180c36e02e4b15b8a842c/bertram_satin_pedersen_luciani_sherman_2007.cellml
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<article>
<articleinfo>
<title>Interaction of glycolysis and mitochondrial respiration in metabolic oscillations of pancreatic islets</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>This CellML model has been coded by translating the authors original XPPAUT.ode file, which can be found at http://www.math.fsu.edu/~bertram/software/islet/BJ_07/mitophan.ode. The model runs in PCEnv in COR and is able to produce the published results. The parameters have been chosen to recreate the bursting behaviour seen in figures 3 and 4 of the original paper. Some equations have inconsistent magnitudes due to the fact that some units are defined in milliseconds whereas others are defined in seconds.</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>Glucose metabolism plays a key signalling role in insulin-secreting pancreatic beta cells. In addition to generating ATP - the ubiquitous form of energy used to fuel many cellular processes - glucose metabolism in pancreatic beta cells is also the means by which blood glucose levels are monitored, ensuring an appropriate level of insulin secretion. ATP-sensitive potassium channels in the plasma membrane are activated by ADP and are inactivated by ATP, therefore a high ATP/ADP ratio results in a reduced number of open, ATP-sensitive, potassium channels. In turn, this results in membrane depolarisation and voltage-sensitive calcium channels open. The resulting influx of calcium ions into the cell cytosol induces insulin secretion, which in a healthy individual typically occurs in oscillatory waves. These can be fast with an oscillatory period of less than a minute, or slow with a duration of 2 to 7 minutes, or they can be a combination of fast and slow waves. This oscillatory pattern of insulin secretion appears to have a physiological function which is of particular interest since it is lost in patients with type II diabetes.</para>
<para>
Although the definitive mechanisms underlying these insulin oscillations are unknown, in the paper described here, Richard Bertram
<emphasis>et al.</emphasis>
suggest that calcium feedback onto ATP production or consumption is responsible for the fast component of the insulin oscillations, while oscillations in the glycolytic pathway are responsible for the slow component. Furthermore, they build these phenomena into a mathematical model that combines a model of mitochondrial metabolism with models of glycolytic oscillations, plasma membrane electrical activity, and calcium handling in the cytosol and endoplasmic reticulum (summarised in the figure below).
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="bertram_2007.png" />
</imageobject>
</mediaobject>
<caption>Schematic diagram of the model components and the variables which are exchanged between the components.</caption>
</informalfigure>
<para>The original paper reference is cited below:</para>
<para>
Interaction of glycolysis and mitochondrial respiration in metabolic oscillations of pancreatic islets, Richard Bertram, Leslie S. Satin, Morten Gram Pedersen, Dan S. Luciani, and Arthur Sherman, 2007,
<emphasis>Biophysical Journal</emphasis>
, 92, 1544-1555.
<ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17172305&query_hl=1&itool=pubmed_docsum">PubMed ID: 17172305</ulink>
</para>
<para>
The authors highlight that the original model code can be downloaded
<ulink url="http://www.math.fsu.edu/~bertram/software/islet/BJ_07/mitophan.ode">here</ulink>
.
</para>
</sect1>
</article>
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<variable cmeta:id="JPFK.atp" name="atp" public_interface="in" units="micromolar" />
<variable cmeta:id="JPFK.weight2" name="weight2" units="dimensionless" />
<variable cmeta:id="JPFK.topa2" name="topa2" units="dimensionless" />
<variable cmeta:id="JPFK.bottom2" name="bottom2" units="dimensionless" />
<variable cmeta:id="JPFK.F6P" name="F6P" public_interface="in" units="micromolar" />
<variable cmeta:id="JPFK.topa3" name="topa3" units="dimensionless" />
<variable cmeta:id="JPFK.weight3" name="weight3" units="dimensionless" />
<variable cmeta:id="JPFK.bottom3" name="bottom3" units="dimensionless" />
<variable cmeta:id="JPFK.f13" initial_value="0.02" name="f13" units="dimensionless" />
<variable cmeta:id="JPFK.f43" initial_value="20" name="f43" units="dimensionless" />
<variable cmeta:id="JPFK.f23" initial_value="0.2" name="f23" units="dimensionless" />
<variable cmeta:id="JPFK.f42" initial_value="20" name="f42" units="dimensionless" />
<variable cmeta:id="JPFK.f41" initial_value="20" name="f41" units="dimensionless" />
<variable cmeta:id="JPFK.weight4" name="weight4" units="dimensionless" />
<variable cmeta:id="JPFK.topa4" name="topa4" units="dimensionless" />
<variable cmeta:id="JPFK.bottom4" name="bottom4" units="dimensionless" />
<variable cmeta:id="JPFK.weight5" name="weight5" units="dimensionless" />
<variable cmeta:id="JPFK.topa5" name="topa5" units="dimensionless" />
<variable cmeta:id="JPFK.bottom5" name="bottom5" units="dimensionless" />
<variable cmeta:id="JPFK.weight6" name="weight6" units="dimensionless" />
<variable cmeta:id="JPFK.topa6" name="topa6" units="dimensionless" />
<variable cmeta:id="JPFK.bottom6" name="bottom6" units="dimensionless" />
<variable cmeta:id="JPFK.weight7" name="weight7" units="dimensionless" />
<variable cmeta:id="JPFK.topa7" name="topa7" units="dimensionless" />
<variable cmeta:id="JPFK.bottom7" name="bottom7" units="dimensionless" />
<variable cmeta:id="JPFK.weight8" name="weight8" units="dimensionless" />
<variable cmeta:id="JPFK.topa8" name="topa8" units="dimensionless" />
<variable cmeta:id="JPFK.bottom8" name="bottom8" units="dimensionless" />
<variable cmeta:id="JPFK.weight9" name="weight9" units="dimensionless" />
<variable cmeta:id="JPFK.topa9" name="topa9" units="dimensionless" />
<variable cmeta:id="JPFK.bottom9" name="bottom9" units="dimensionless" />
<variable cmeta:id="JPFK.weight10" name="weight10" units="dimensionless" />
<variable cmeta:id="JPFK.topa10" name="topa10" units="dimensionless" />
<variable cmeta:id="JPFK.bottom10" name="bottom10" units="dimensionless" />
<variable cmeta:id="JPFK.weight11" name="weight11" units="dimensionless" />
<variable cmeta:id="JPFK.topa11" name="topa11" units="dimensionless" />
<variable cmeta:id="JPFK.bottom11" name="bottom11" units="dimensionless" />
<variable cmeta:id="JPFK.weight12" name="weight12" units="dimensionless" />
<variable cmeta:id="JPFK.topa12" name="topa12" units="dimensionless" />
<variable cmeta:id="JPFK.bottom12" name="bottom12" units="dimensionless" />
<variable cmeta:id="JPFK.weight13" name="weight13" units="dimensionless" />
<variable cmeta:id="JPFK.topa13" name="topa13" units="dimensionless" />
<variable cmeta:id="JPFK.bottom13" name="bottom13" units="dimensionless" />
<variable cmeta:id="JPFK.weight14" name="weight14" units="dimensionless" />
<variable cmeta:id="JPFK.topa14" name="topa14" units="dimensionless" />
<variable cmeta:id="JPFK.bottom14" name="bottom14" units="dimensionless" />
<variable cmeta:id="JPFK.weight15" name="weight15" units="dimensionless" />
<variable cmeta:id="JPFK.topa15" name="topa15" units="dimensionless" />
<variable cmeta:id="JPFK.bottom15" name="bottom15" units="dimensionless" />
<variable cmeta:id="JPFK.weight16" name="weight16" units="dimensionless" />
<variable cmeta:id="JPFK.topa16" name="topa16" units="dimensionless" />
<variable cmeta:id="JPFK.bottom16" name="bottom16" units="dimensionless" />
<variable cmeta:id="JPFK.topb" name="topb" units="dimensionless" />
<variable cmeta:id="JPFK.FBP" name="FBP" public_interface="in" units="micromolar" />
<variable cmeta:id="JPFK.AMP" name="AMP" public_interface="in" units="micromolar" />
<variable cmeta:id="JPFK.lambda" initial_value="0.06" name="lambda" units="dimensionless" />
<variable cmeta:id="JPFK.kappa" name="kappa" public_interface="in" units="dimensionless" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="pfk">
<apply>
<eq />
<ci>JPFK_ms</ci>
<apply>
<times />
<ci>kappa</ci>
<ci>JPFK</ci>
</apply>
</apply>
<apply>
<eq />
<ci>JPFK</ci>
<apply>
<divide />
<apply>
<plus />
<apply>
<times />
<ci>lambda</ci>
<ci>VmaxPFK</ci>
<ci>topa16</ci>
</apply>
<apply>
<times />
<ci>VmaxPFK</ci>
<ci>topb</ci>
</apply>
</apply>
<ci>bottom16</ci>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="0001">
<apply>
<eq />
<ci>weight2</ci>
<apply>
<divide />
<apply>
<power />
<ci>atp</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
<apply>
<times />
<ci>k4</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="micromolar">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>topa2</ci>
<ci>topa1</ci>
</apply>
<apply>
<eq />
<ci>bottom2</ci>
<apply>
<plus />
<ci>bottom1</ci>
<ci>weight2</ci>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="0010">
<apply>
<eq />
<ci>weight3</ci>
<apply>
<divide />
<apply>
<power />
<ci>F6P</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
<apply>
<times />
<ci>k3</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="micromolar">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>topa3</ci>
<apply>
<plus />
<ci>topa2</ci>
<ci>weight3</ci>
</apply>
</apply>
<apply>
<eq />
<ci>bottom3</ci>
<apply>
<plus />
<ci>bottom2</ci>
<ci>weight3</ci>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="0011">
<apply>
<eq />
<ci>weight4</ci>
<apply>
<divide />
<apply>
<power />
<apply>
<times />
<ci>F6P</ci>
<ci>atp</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
<apply>
<times />
<ci>f43</ci>
<ci>k3</ci>
<ci>k4</ci>
<apply>
<power />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="micromolar">1</cn>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>topa4</ci>
<apply>
<plus />
<ci>topa3</ci>
<ci>weight4</ci>
</apply>
</apply>
<apply>
<eq />
<ci>bottom4</ci>
<apply>
<plus />
<ci>bottom3</ci>
<ci>weight4</ci>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="0100">
<apply>
<eq />
<ci>weight5</ci>
<apply>
<divide />
<ci>FBP</ci>
<ci>k2</ci>
</apply>
</apply>
<apply>
<eq />
<ci>topa5</ci>
<ci>topa4</ci>
</apply>
<apply>
<eq />
<ci>bottom5</ci>
<apply>
<plus />
<ci>bottom4</ci>
<ci>weight5</ci>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="0101">
<apply>
<eq />
<ci>weight6</ci>
<apply>
<divide />
<apply>
<times />
<ci>FBP</ci>
<apply>
<power />
<ci>atp</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<times />
<ci>k2</ci>
<ci>k4</ci>
<ci>f42</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="micromolar">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>topa6</ci>
<ci>topa5</ci>
</apply>
<apply>
<eq />
<ci>bottom6</ci>
<apply>
<plus />
<ci>bottom5</ci>
<ci>weight6</ci>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="0110">
<apply>
<eq />
<ci>weight7</ci>
<apply>
<divide />
<apply>
<times />
<ci>FBP</ci>
<apply>
<power />
<ci>F6P</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<times />
<ci>k2</ci>
<ci>k3</ci>
<ci>f23</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="micromolar">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>topa7</ci>
<apply>
<plus />
<ci>topa6</ci>
<ci>weight7</ci>
</apply>
</apply>
<apply>
<eq />
<ci>bottom7</ci>
<apply>
<plus />
<ci>bottom6</ci>
<ci>weight7</ci>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="0111">
<apply>
<eq />
<ci>weight8</ci>
<apply>
<divide />
<apply>
<times />
<ci>FBP</ci>
<apply>
<power />
<ci>F6P</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
<apply>
<power />
<ci>atp</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<times />
<ci>k2</ci>
<ci>k3</ci>
<ci>k4</ci>
<ci>f23</ci>
<ci>f42</ci>
<ci>f43</ci>
<apply>
<power />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="micromolar">1</cn>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>topa8</ci>
<apply>
<plus />
<ci>topa7</ci>
<ci>weight8</ci>
</apply>
</apply>
<apply>
<eq />
<ci>bottom8</ci>
<apply>
<plus />
<ci>bottom7</ci>
<ci>weight8</ci>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="1000">
<apply>
<eq />
<ci>weight9</ci>
<apply>
<divide />
<ci>AMP</ci>
<ci>k1</ci>
</apply>
</apply>
<apply>
<eq />
<ci>topa9</ci>
<ci>topa8</ci>
</apply>
<apply>
<eq />
<ci>bottom9</ci>
<apply>
<plus />
<ci>bottom8</ci>
<ci>weight9</ci>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="1001">
<apply>
<eq />
<ci>weight10</ci>
<apply>
<divide />
<apply>
<times />
<ci>AMP</ci>
<apply>
<power />
<ci>atp</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<times />
<ci>k1</ci>
<ci>k4</ci>
<ci>f41</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="micromolar">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>topa10</ci>
<ci>topa9</ci>
</apply>
<apply>
<eq />
<ci>bottom10</ci>
<apply>
<plus />
<ci>bottom9</ci>
<ci>weight10</ci>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="1010">
<apply>
<eq />
<ci>weight11</ci>
<apply>
<divide />
<apply>
<times />
<ci>AMP</ci>
<apply>
<power />
<ci>F6P</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<times />
<ci>k1</ci>
<ci>k3</ci>
<ci>f13</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="micromolar">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>topa11</ci>
<apply>
<plus />
<ci>topa10</ci>
<ci>weight11</ci>
</apply>
</apply>
<apply>
<eq />
<ci>bottom11</ci>
<apply>
<plus />
<ci>bottom10</ci>
<ci>weight11</ci>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="1011">
<apply>
<eq />
<ci>weight12</ci>
<apply>
<divide />
<apply>
<times />
<ci>AMP</ci>
<apply>
<power />
<ci>F6P</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
<apply>
<power />
<ci>atp</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<times />
<ci>k1</ci>
<ci>k3</ci>
<ci>k4</ci>
<ci>f13</ci>
<ci>f41</ci>
<ci>f43</ci>
<apply>
<power />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="micromolar">1</cn>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>topa12</ci>
<apply>
<plus />
<ci>topa11</ci>
<ci>weight12</ci>
</apply>
</apply>
<apply>
<eq />
<ci>bottom12</ci>
<apply>
<plus />
<ci>bottom11</ci>
<ci>weight12</ci>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="1100">
<apply>
<eq />
<ci>weight13</ci>
<apply>
<divide />
<apply>
<times />
<ci>AMP</ci>
<ci>FBP</ci>
</apply>
<apply>
<times />
<ci>k1</ci>
<ci>k2</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>topa13</ci>
<ci>topa12</ci>
</apply>
<apply>
<eq />
<ci>bottom13</ci>
<apply>
<plus />
<ci>bottom12</ci>
<ci>weight13</ci>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="1101">
<apply>
<eq />
<ci>weight14</ci>
<apply>
<divide />
<apply>
<times />
<ci>AMP</ci>
<ci>FBP</ci>
<apply>
<power />
<ci>atp</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<times />
<ci>k1</ci>
<ci>k2</ci>
<ci>k4</ci>
<ci>f42</ci>
<ci>f41</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="micromolar">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>topa14</ci>
<ci>topa13</ci>
</apply>
<apply>
<eq />
<ci>bottom14</ci>
<apply>
<plus />
<ci>bottom13</ci>
<ci>weight14</ci>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="1110">
<apply>
<eq />
<ci>weight15</ci>
<apply>
<divide />
<apply>
<times />
<ci>AMP</ci>
<ci>FBP</ci>
<apply>
<power />
<ci>F6P</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<times />
<ci>k1</ci>
<ci>k2</ci>
<ci>k3</ci>
<ci>f23</ci>
<ci>f13</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="micromolar">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>topa15</ci>
<ci>topa14</ci>
</apply>
<apply>
<eq />
<ci>bottom15</ci>
<apply>
<plus />
<ci>bottom14</ci>
<ci>weight15</ci>
</apply>
</apply>
<apply>
<eq />
<ci>topb</ci>
<ci>weight15</ci>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="1111">
<apply>
<eq />
<ci>weight16</ci>
<apply>
<divide />
<apply>
<times />
<ci>AMP</ci>
<ci>FBP</ci>
<apply>
<power />
<ci>F6P</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
<apply>
<power />
<ci>atp</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<times />
<ci>k1</ci>
<ci>k2</ci>
<ci>k3</ci>
<ci>k4</ci>
<ci>f23</ci>
<ci>f13</ci>
<ci>f42</ci>
<ci>f41</ci>
<ci>f43</ci>
<apply>
<power />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="micromolar">1</cn>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>topa16</ci>
<apply>
<plus />
<ci>topa15</ci>
<ci>weight16</ci>
</apply>
</apply>
<apply>
<eq />
<ci>bottom16</ci>
<apply>
<plus />
<ci>bottom15</ci>
<ci>weight16</ci>
</apply>
</apply>
</math>
</component>
<component name="JPDH" cmeta:id="JPDH">
<variable cmeta:id="JPDH.JPDH" name="JPDH" public_interface="out" units="micromolar_millisecond" />
<variable cmeta:id="JPDH.p1" initial_value="400.0" name="p1" units="dimensionless" />
<variable cmeta:id="JPDH.p2" initial_value="1.0" name="p2" units="dimensionless" />
<variable cmeta:id="JPDH.p3" initial_value="0.01" name="p3" units="micromolar" />
<variable cmeta:id="JPDH.JGPDHbas" initial_value="0.0005" name="JGPDHbas" units="micromolar_millisecond" />
<variable cmeta:id="JPDH.NADm" name="NADm" public_interface="in" units="millimolar" />
<variable cmeta:id="JPDH.Cam" name="Cam" public_interface="in" units="micromolar" />
<variable cmeta:id="JPDH.NADHm" name="NADHm" public_interface="in" units="millimolar" />
<variable cmeta:id="JPDH.JGPDH" name="JGPDH" public_interface="in" units="micromolar_millisecond" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>JPDH</ci>
<apply>
<times />
<apply>
<divide />
<ci>p1</ci>
<apply>
<plus />
<ci>p2</ci>
<apply>
<divide />
<ci>NADHm</ci>
<ci>NADm</ci>
</apply>
</apply>
</apply>
<apply>
<divide />
<ci>Cam</ci>
<apply>
<plus />
<ci>p3</ci>
<ci>Cam</ci>
</apply>
</apply>
<apply>
<plus />
<ci>JGPDH</ci>
<ci>JGPDHbas</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="NADHm" cmeta:id="NADHm">
<variable cmeta:id="NADHm_NADHm" initial_value="0.4" name="NADHm" public_interface="out" units="millimolar" />
<variable cmeta:id="NADHm.gamma" name="gamma" public_interface="in" units="dimensionless" />
<variable cmeta:id="NADHm.JPDH" name="JPDH" public_interface="in" units="micromolar_millisecond" />
<variable cmeta:id="NADHm.JO" name="JO" public_interface="in" units="micromolar_millisecond" />
<variable cmeta:id="NADHm.time" name="time" public_interface="in" units="millisecond" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>NADHm</ci>
</apply>
<apply>
<times />
<ci>gamma</ci>
<apply>
<minus />
<ci>JPDH</ci>
<ci>JO</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="JO" cmeta:id="JO">
<variable cmeta:id="JO.JO" name="JO" public_interface="out" units="micromolar_millisecond" />
<variable cmeta:id="JO.p4" initial_value="0.6" name="p4" units="micromolar_millisecond" />
<variable cmeta:id="JO.p5" initial_value="0.1" name="p5" units="millimolar" />
<variable cmeta:id="JO.p6" initial_value="177.0" name="p6" units="millivolt" />
<variable cmeta:id="JO.p7" initial_value="5.0" name="p7" units="millivolt" />
<variable cmeta:id="JO.NADHm" name="NADHm" public_interface="in" units="millimolar" />
<variable cmeta:id="JO.delta_psi" name="delta_psi" public_interface="in" units="millivolt" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>JO</ci>
<apply>
<divide />
<apply>
<times />
<ci>p4</ci>
<apply>
<divide />
<ci>NADHm</ci>
<apply>
<plus />
<ci>p5</ci>
<ci>NADHm</ci>
</apply>
</apply>
</apply>
<apply>
<plus />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.0</cn>
<apply>
<exp />
<apply>
<divide />
<apply>
<minus />
<ci>delta_psi</ci>
<ci>p6</ci>
</apply>
<ci>p7</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="NADm" cmeta:id="NADm">
<variable cmeta:id="NADm.NADm" name="NADm" public_interface="out" units="millimolar" />
<variable cmeta:id="NADm.NADmtot" initial_value="10.0" name="NADmtot" units="millimolar" />
<variable cmeta:id="NADm.NADHm" name="NADHm" public_interface="in" units="millimolar" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>NADm</ci>
<apply>
<minus />
<ci>NADmtot</ci>
<ci>NADHm</ci>
</apply>
</apply>
</math>
</component>
<component name="delta_psi" cmeta:id="delta_psi">
<variable cmeta:id="delta_psi_delta_psi" initial_value="164.0" name="delta_psi" public_interface="out" units="millivolt" />
<variable cmeta:id="delta_psi.Cmito" initial_value="1.8" name="Cmito" units="micromolar_millivolt" />
<variable cmeta:id="delta_psi.JHres" name="JHres" public_interface="in" units="micromolar_millisecond" />
<variable cmeta:id="delta_psi.JHatp" name="JHatp" public_interface="in" units="micromolar_millisecond" />
<variable cmeta:id="delta_psi.JANT" name="JANT" public_interface="in" units="micromolar_millisecond" />
<variable cmeta:id="delta_psi.JHleak" name="JHleak" public_interface="in" units="micromolar_millisecond" />
<variable cmeta:id="delta_psi.JNaCa" name="JNaCa" public_interface="in" units="micromolar_millisecond" />
<variable cmeta:id="delta_psi.Juni" name="Juni" public_interface="in" units="micromolar_millisecond" />
<variable cmeta:id="delta_psi.time" name="time" public_interface="in" units="millisecond" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>delta_psi</ci>
</apply>
<apply>
<divide />
<apply>
<minus />
<ci>JHres</ci>
<apply>
<plus />
<ci>JHatp</ci>
<ci>JANT</ci>
<ci>JHleak</ci>
<ci>JNaCa</ci>
<apply>
<times />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2.0</cn>
<ci>Juni</ci>
</apply>
</apply>
</apply>
<ci>Cmito</ci>
</apply>
</apply>
</math>
</component>
<component name="JHres" cmeta:id="JHres">
<variable cmeta:id="JHres.JHres" name="JHres" public_interface="out" units="micromolar_millisecond" />
<variable cmeta:id="JHres.p8" initial_value="7.0" name="p8" units="micromolar_millisecond" />
<variable cmeta:id="JHres.p9" initial_value="0.1" name="p9" units="millimolar" />
<variable cmeta:id="JHres.p10" initial_value="177.0" name="p10" units="millivolt" />
<variable cmeta:id="JHres.p11" initial_value="5.0" name="p11" units="millivolt" />
<variable cmeta:id="JHres.NADHm" name="NADHm" public_interface="in" units="millimolar" />
<variable cmeta:id="JHres.delta_psi" name="delta_psi" public_interface="in" units="millivolt" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>JHres</ci>
<apply>
<divide />
<apply>
<times />
<ci>p8</ci>
<apply>
<divide />
<ci>NADHm</ci>
<apply>
<plus />
<ci>p9</ci>
<ci>NADHm</ci>
</apply>
</apply>
</apply>
<apply>
<plus />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.0</cn>
<apply>
<exp />
<apply>
<divide />
<apply>
<minus />
<ci>delta_psi</ci>
<ci>p10</ci>
</apply>
<ci>p11</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="JF1F0" cmeta:id="JF1F0">
<variable cmeta:id="JF1F0.JF1F0" name="JF1F0" public_interface="out" units="micromolar_millisecond" />
<variable cmeta:id="JF1F0.p13" initial_value="10.0" name="p13" units="millimolar" />
<variable cmeta:id="JF1F0.p14" initial_value="190.0" name="p14" units="millivolt" />
<variable cmeta:id="JF1F0.p15" initial_value="8.5" name="p15" units="millivolt" />
<variable cmeta:id="JF1F0.p16" initial_value="35.0" name="p16" units="micromolar_millisecond" />
<variable cmeta:id="JF1F0.ATPm" name="ATPm" public_interface="in" units="millimolar" />
<variable cmeta:id="JF1F0.delta_psi" name="delta_psi" public_interface="in" units="millivolt" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>JF1F0</ci>
<apply>
<divide />
<apply>
<divide />
<apply>
<times />
<ci>p16</ci>
<ci>p13</ci>
</apply>
<apply>
<plus />
<ci>p13</ci>
<ci>ATPm</ci>
</apply>
</apply>
<apply>
<plus />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.0</cn>
<apply>
<exp />
<apply>
<divide />
<apply>
<minus />
<ci>p14</ci>
<ci>delta_psi</ci>
</apply>
<ci>p15</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="JHatp" cmeta:id="JHatp">
<variable cmeta:id="JHatp.JHatp" name="JHatp" public_interface="out" units="micromolar_millisecond" />
<variable cmeta:id="JHatp.JF1F0" name="JF1F0" public_interface="in" units="micromolar_millisecond" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>JHatp</ci>
<apply>
<times />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3.0</cn>
<ci>JF1F0</ci>
</apply>
</apply>
</math>
</component>
<component name="JGK" cmeta:id="JGK">
<variable cmeta:id="JGK.JGK_ms" name="JGK_ms" public_interface="out" units="micromolar_millisecond" />
<variable cmeta:id="JGK.JGK" initial_value="0.4" name="JGK" units="micromolar_second" />
<variable cmeta:id="JGK.kappa" name="kappa" public_interface="in" units="dimensionless" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>JGK_ms</ci>
<apply>
<times />
<ci>kappa</ci>
<ci>JGK</ci>
</apply>
</apply>
</math>
</component>
<component name="JHleak" cmeta:id="JHleak">
<variable cmeta:id="JHleak.JHleak" name="JHleak" public_interface="out" units="micromolar_millisecond" />
<variable cmeta:id="JHleak.p17" initial_value="0.002" name="p17" units="micromolar_millisecond_millivolt" />
<variable cmeta:id="JHleak.p18" initial_value="-0.03" name="p18" units="micromolar_millisecond" />
<variable cmeta:id="JHleak.delta_psi" name="delta_psi" public_interface="in" units="millivolt" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>JHleak</ci>
<apply>
<plus />
<apply>
<times />
<ci>p17</ci>
<ci>delta_psi</ci>
</apply>
<ci>p18</ci>
</apply>
</apply>
</math>
</component>
<component name="JANT" cmeta:id="JANT">
<variable cmeta:id="JANT.JANT" name="JANT" public_interface="out" units="micromolar_millisecond" />
<variable cmeta:id="JANT.p19" initial_value="0.35" name="p19" units="micromolar_millisecond" />
<variable cmeta:id="JANT.p20" initial_value="2.0" name="p20" units="dimensionless" />
<variable cmeta:id="JANT.FRT" initial_value="0.037410133" name="FRT" units="per_millivolt" />
<variable cmeta:id="JANT.RATm" name="RATm" public_interface="in" units="dimensionless" />
<variable cmeta:id="JANT.delta_psi" name="delta_psi" public_interface="in" units="millivolt" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>JANT</ci>
<apply>
<times />
<ci>p19</ci>
<apply>
<divide />
<apply>
<divide />
<ci>RATm</ci>
<apply>
<plus />
<ci>RATm</ci>
<ci>p20</ci>
</apply>
</apply>
<apply>
<exp />
<apply>
<times />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">-0.5</cn>
<ci>FRT</ci>
<ci>delta_psi</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="RATm">
<variable cmeta:id="RATm.RATm" name="RATm" public_interface="out" units="dimensionless" />
<variable cmeta:id="RATm.ATPm" name="ATPm" public_interface="in" units="millimolar" />
<variable cmeta:id="RATm.ADPm" name="ADPm" public_interface="in" units="millimolar" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>RATm</ci>
<apply>
<divide />
<ci>ATPm</ci>
<ci>ADPm</ci>
</apply>
</apply>
</math>
</component>
<component name="Juni" cmeta:id="Juni">
<variable cmeta:id="Juni.Juni" name="Juni" public_interface="out" units="micromolar_millisecond" />
<variable cmeta:id="Juni.p21" initial_value="0.04" name="p21" units="per_micromolar_millisecond_millivolt" />
<variable cmeta:id="Juni.p22" initial_value="1.1" name="p22" units="second_order_rate_constant" />
<variable cmeta:id="Juni.c" name="c" public_interface="in" units="micromolar" />
<variable cmeta:id="Juni.delta_psi" name="delta_psi" public_interface="in" units="millivolt" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>Juni</ci>
<apply>
<times />
<apply>
<minus />
<apply>
<times />
<ci>p21</ci>
<ci>delta_psi</ci>
</apply>
<ci>p22</ci>
</apply>
<apply>
<power />
<ci>c</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2.0</cn>
</apply>
</apply>
</apply>
</math>
</component>
<component name="JNaCa" cmeta:id="JNaCa">
<variable cmeta:id="JNaCa.JNaCa" name="JNaCa" public_interface="out" units="micromolar_millisecond" />
<variable cmeta:id="JNaCa.p23" initial_value="0.01" name="p23" units="micromolar_millisecond" />
<variable cmeta:id="JNaCa.p24" initial_value="0.016" name="p24" units="per_millivolt" />
<variable cmeta:id="JNaCa.c" name="c" public_interface="in" units="micromolar" />
<variable cmeta:id="JNaCa.Cam" name="Cam" public_interface="in" units="micromolar" />
<variable cmeta:id="JNaCa.delta_psi" name="delta_psi" public_interface="in" units="millivolt" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>JNaCa</ci>
<apply>
<times />
<apply>
<divide />
<ci>p23</ci>
<ci>c</ci>
</apply>
<ci>Cam</ci>
<apply>
<exp />
<apply>
<times />
<ci>p24</ci>
<ci>delta_psi</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Cam" cmeta:id="Cam">
<variable cmeta:id="Cam_Cam" initial_value="0.2" name="Cam" public_interface="out" units="micromolar" />
<variable cmeta:id="Cam.fmito" initial_value="0.01" name="fmito" units="dimensionless" />
<variable cmeta:id="Cam.Jmito" name="Jmito" public_interface="in" units="micromolar_millisecond" />
<variable cmeta:id="Cam.time" name="time" public_interface="in" units="millisecond" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>Cam</ci>
</apply>
<apply>
<times />
<apply>
<minus />
<ci>fmito</ci>
</apply>
<ci>Jmito</ci>
</apply>
</apply>
</math>
</component>
<component name="Jmito">
<variable cmeta:id="Jmito.Jmito" name="Jmito" public_interface="out" units="micromolar_millisecond" />
<variable cmeta:id="Jmito.JNaCa" name="JNaCa" public_interface="in" units="micromolar_millisecond" />
<variable cmeta:id="Jmito.Juni" name="Juni" public_interface="in" units="micromolar_millisecond" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>Jmito</ci>
<apply>
<minus />
<ci>JNaCa</ci>
<ci>Juni</ci>
</apply>
</apply>
</math>
</component>
<component name="ADPm" cmeta:id="ADPm">
<variable cmeta:id="ADPm_ADPm" initial_value="11.1" name="ADPm" public_interface="out" units="millimolar" />
<variable cmeta:id="ADPm.gamma" name="gamma" public_interface="in" units="dimensionless" />
<variable cmeta:id="ADPm.JANT" name="JANT" public_interface="in" units="micromolar_millisecond" />
<variable cmeta:id="ADPm.JF1F0" name="JF1F0" public_interface="in" units="micromolar_millisecond" />
<variable cmeta:id="ADPm.time" name="time" public_interface="in" units="millisecond" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>ADPm</ci>
</apply>
<apply>
<times />
<ci>gamma</ci>
<apply>
<minus />
<ci>JANT</ci>
<ci>JF1F0</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="ATPm" cmeta:id="ATPm">
<variable cmeta:id="ATPm.ATPm" name="ATPm" public_interface="out" units="millimolar" />
<variable cmeta:id="ATPm.Amtot" initial_value="15.0" name="Amtot" units="millimolar" />
<variable cmeta:id="ATPm.ADPm" name="ADPm" public_interface="in" units="millimolar" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>ATPm</ci>
<apply>
<minus />
<ci>Amtot</ci>
<ci>ADPm</ci>
</apply>
</apply>
</math>
</component>
<component name="adp" cmeta:id="adp">
<variable cmeta:id="adp_adp" initial_value="1137.0" name="adp" public_interface="out" units="micromolar" />
<variable cmeta:id="adp.delta" name="delta" public_interface="in" units="dimensionless" />
<variable cmeta:id="adp.Jhyd" name="Jhyd" public_interface="in" units="micromolar_millisecond" />
<variable cmeta:id="adp.JANT" name="JANT" public_interface="in" units="micromolar_millisecond" />
<variable cmeta:id="adp.time" name="time" public_interface="in" units="millisecond" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>adp</ci>
</apply>
<apply>
<plus />
<apply>
<times />
<apply>
<minus />
<ci>delta</ci>
</apply>
<ci>JANT</ci>
</apply>
<ci>Jhyd</ci>
</apply>
</apply>
</math>
</component>
<component name="Jhyd" cmeta:id="Jhyd">
<variable cmeta:id="Jhyd.Jhyd" name="Jhyd" public_interface="out" units="micromolar_millisecond" />
<variable cmeta:id="Jhyd.khyd" initial_value="0.00005" name="khyd" units="second_order_rate_constant" />
<variable cmeta:id="Jhyd.khydbas" initial_value="0.00005" name="khydbas" units="first_order_rate_constant" />
<variable cmeta:id="Jhyd.c" name="c" public_interface="in" units="micromolar" />
<variable cmeta:id="Jhyd.atp" name="atp" public_interface="in" units="micromolar" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>Jhyd</ci>
<apply>
<times />
<apply>
<plus />
<apply>
<times />
<ci>khyd</ci>
<ci>c</ci>
</apply>
<ci>khydbas</ci>
</apply>
<ci>atp</ci>
</apply>
</apply>
</math>
</component>
<component name="atp" cmeta:id="atp">
<variable cmeta:id="atp_atp" name="atp" public_interface="out" units="micromolar" />
<variable cmeta:id="atp.atot" initial_value="2500.0" name="atot" units="micromolar" />
<variable cmeta:id="atp.adp" name="adp" public_interface="in" units="micromolar" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>atp</ci>
<apply>
<minus />
<ci>atot</ci>
<ci>adp</ci>
</apply>
</apply>
</math>
</component>
<component name="c" cmeta:id="c">
<variable cmeta:id="c.c" initial_value="0.17" name="c" public_interface="out" units="micromolar" />
<variable cmeta:id="c.fcyt" initial_value="0.01" name="fcyt" units="dimensionless" />
<variable cmeta:id="c.delta" name="delta" public_interface="in" units="dimensionless" />
<variable cmeta:id="c.Jer" name="Jer" public_interface="in" units="micromolar_millisecond" />
<variable cmeta:id="c.Jmem" name="Jmem" public_interface="in" units="micromolar_millisecond" />
<variable cmeta:id="c.Jmito" name="Jmito" public_interface="in" units="micromolar_millisecond" />
<variable cmeta:id="c.time" name="time" public_interface="in" units="millisecond" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>c</ci>
</apply>
<apply>
<times />
<ci>fcyt</ci>
<apply>
<plus />
<ci>Jmem</ci>
<ci>Jer</ci>
<apply>
<times />
<ci>delta</ci>
<ci>Jmito</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Jmem" cmeta:id="Jmem">
<variable cmeta:id="Jmem.Jmem" name="Jmem" public_interface="out" units="micromolar_millisecond" />
<variable cmeta:id="Jmem.kPMCA" initial_value="0.1" name="kPMCA" units="first_order_rate_constant" />
<variable cmeta:id="Jmem.alpha" initial_value="4.5E-6" name="alpha" units="micromolar_millisecond_femtoampere" />
<variable cmeta:id="Jmem.Cbas" initial_value="0.05" name="Cbas" units="micromolar" />
<variable cmeta:id="Jmem.c" name="c" public_interface="in" units="micromolar" />
<variable cmeta:id="Jmem.Ica" name="Ica" public_interface="in" units="femtoampere" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>Jmem</ci>
<apply>
<minus />
<apply>
<plus />
<apply>
<times />
<ci>alpha</ci>
<ci>Ica</ci>
</apply>
<apply>
<times />
<ci>kPMCA</ci>
<apply>
<minus />
<ci>c</ci>
<ci>Cbas</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Jleak" cmeta:id="Jleak">
<variable cmeta:id="Jleak.Jleak" name="Jleak" public_interface="out" units="micromolar_millisecond" />
<variable cmeta:id="Jleak.pleak" initial_value="0.0002" name="pleak" units="first_order_rate_constant" />
<variable cmeta:id="Jleak.c" name="c" public_interface="in" units="micromolar" />
<variable cmeta:id="Jleak.Caer" name="Caer" public_interface="in" units="micromolar" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>Jleak</ci>
<apply>
<times />
<ci>pleak</ci>
<apply>
<minus />
<ci>Caer</ci>
<ci>c</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="JSERCA" cmeta:id="JSERCA">
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<rdf:value xml:lang="en">This CellML model has been coded by translating the authors original XPPAUT .ode file, which can be found at http://www.math.fsu.edu/~bertram/software/islet/BJ_07/mitophan.ode . The model runs in PCEnv and is able to produce the published results. The parameters have been chosen to recreate the bursting behaviour seen in figures 3 and 4 of the original paper.</rdf:value>
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<publisher xml:lang="en">The University of Auckland, Bioengineering Institute</publisher>
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<dcterms:description>Mitochondrial inner membrane potential changes</dcterms:description>
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<rdf:Description rdf:about="#membrane.Ikca">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_3">
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<rdf:Description rdf:about="#process_2">
<semsim:hasMediatorParticipant>
<rdf:Description rdf:about="#mediator_2">
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<rdf:Description rdf:about="#entity_11">
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/uniprot/Q62976" />
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<rdf:Description rdf:about="#source_4" semsim:hasMultiplier="1.0">
<semsim:hasPhysicalEntityReference>
<rdf:Description rdf:about="#entity_9">
<ro:part_of>
<rdf:Description rdf:about="#entity_10">
<semsim:name>Electrical/Calcium compartment</semsim:name>
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</ro:part_of>
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</rdf:Description>
</semsim:hasPhysicalEntityReference>
</rdf:Description>
</semsim:hasSourceParticipant>
<semsim:name>Calcium-activated K+ current</semsim:name>
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<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00318" />
</rdf:Description>
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<dcterms:description>Calcium activated K+ current (K+ is activated by cystolic Ca2+).</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Ikca.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#JNaCa.Cam">
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<rdf:Description rdf:about="#property_71">
<semsim:physicalPropertyOf rdf:resource="#entity_28" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
</rdf:Description>
<rdf:Description rdf:about="#c.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#Ikatp.adp">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_19">
<semsim:physicalPropertyOf rdf:resource="#entity_17" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
</rdf:Description>
<rdf:Description rdf:about="#Jer.JSERCA">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_102">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#process_14">
<semsim:hasSinkParticipant>
<rdf:Description rdf:about="#sink_7" semsim:hasMultiplier="1.0">
<semsim:hasPhysicalEntityReference rdf:resource="#entity_43" />
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</semsim:hasSinkParticipant>
<semsim:hasSourceParticipant>
<rdf:Description rdf:about="#source_15" semsim:hasMultiplier="1.0">
<semsim:hasPhysicalEntityReference rdf:resource="#entity_36" />
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</semsim:hasSourceParticipant>
<semsim:name>Flux of Ca2+ into the ER from the cytosol through SERCA</semsim:name>
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<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
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<dcterms:description>Flux into the ER from the cytosol is through SERCA</dcterms:description>
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<rdf:Description rdf:about="#Cam_Cam">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_73">
<semsim:physicalPropertyOf rdf:resource="#entity_28" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
</rdf:Description>
<rdf:Description rdf:about="#Jhyd">
<title xml:lang="en">Jhyd</title>
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</rdf:Description>
<rdf:Description rdf:about="#Ikatp.atp">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_18">
<semsim:physicalPropertyOf rdf:resource="#entity_16" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
</rdf:Description>
<rdf:Description rdf:about="#c.c">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_89">
<semsim:physicalPropertyOf rdf:resource="#entity_13" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
</rdf:Description>
<rdf:Description rdf:about="#Juni">
<title xml:lang="en">Juni</title>
<dcterms:alternative xml:lang="en">calcium flux into the mitochondria through a calcium uniporter</dcterms:alternative>
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<rdf:Description rdf:about="#JF1F0.ATPm">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_56">
<semsim:physicalPropertyOf rdf:resource="#entity_41" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
</rdf:Description>
<rdf:Description rdf:about="#JPFK.atp">
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<rdf:Description rdf:about="#property_29">
<semsim:physicalPropertyOf rdf:resource="#entity_16" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
</rdf:Description>
<rdf:Description rdf:about="#JANT.delta_psi">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_63">
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00378" />
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<dcterms:description>Mitochondrial inner membrane potential changes</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#RATm.ATPm">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_64">
<semsim:physicalPropertyOf rdf:resource="#entity_41" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
</rdf:Description>
<rdf:Description rdf:about="#Ikca.Ikca">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_11">
<semsim:physicalPropertyOf rdf:resource="#process_2" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00318" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Calcium activated K+ current (K+ is activated by cystolic Ca2+).</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Jmem">
<title xml:lang="en">Jmem</title>
<dcterms:alternative xml:lang="en">rate of calcium flux across the plasma membrane</dcterms:alternative>
</rdf:Description>
<rdf:Description rdf:about="#Ica.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#JGPDH_JGPDH">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_21">
<semsim:physicalPropertyOf rdf:resource="#process_4" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
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</semsim:isComputationalComponentFor>
</rdf:Description>
<rdf:Description rdf:about="#Caer.Jer">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_104">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#process_11">
<semsim:hasSourceParticipant>
<rdf:Description rdf:about="#source_12" semsim:hasMultiplier="1.0">
<semsim:hasPhysicalEntityReference rdf:resource="#entity_43" />
</rdf:Description>
</semsim:hasSourceParticipant>
<semsim:name>Flux of calcium out of the endoplasmic reticulum</semsim:name>
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<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Flux of calcium out of the endoplasmic reticulun</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#adp.JANT">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_83">
<semsim:physicalPropertyOf rdf:resource="#process_7" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
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</semsim:isComputationalComponentFor>
</rdf:Description>
<rdf:Description rdf:about="#adp_adp">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_81">
<semsim:physicalPropertyOf rdf:resource="#entity_17" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
</rdf:Description>
<rdf:Description rdf:about="#JPDH.Cam">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_34">
<semsim:physicalPropertyOf rdf:resource="#entity_28" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
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</semsim:isComputationalComponentFor>
</rdf:Description>
<rdf:Description rdf:about="#JNaCa">
<title xml:lang="en">JNaCa</title>
<dcterms:alternative xml:lang="en">calcium flux out of the mitochondria into the cytosol through the sodium-calcium ion exchanger</dcterms:alternative>
</rdf:Description>
<rdf:Description rdf:about="#JF1F0">
<title xml:lang="en">JF1F0</title>
<dcterms:alternative xml:lang="en">rate of the F1F0 ATP synthase catalysed reaction</dcterms:alternative>
</rdf:Description>
<rdf:Description rdf:about="#JHres">
<title xml:lang="en">JHres</title>
<dcterms:alternative xml:lang="en">flux through respiration-driven proton pumps</dcterms:alternative>
</rdf:Description>
<rdf:Description rdf:about="#NADHm.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#NADHm">
<title xml:lang="en">NADHm</title>
<dcterms:alternative xml:lang="en">mitochondrial NADH</dcterms:alternative>
</rdf:Description>
<rdf:Description rdf:about="#Juni.Juni">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_66">
<semsim:physicalPropertyOf rdf:resource="#process_9" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Flux through calcium uniporters</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#JO.NADHm">
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<rdf:Description rdf:about="#property_41">
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<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
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</rdf:Description>
<rdf:Description rdf:about="#Ikatp.Ikatp">
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<rdf:Description rdf:about="#property_14">
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<rdf:Description rdf:about="#process_3">
<semsim:hasMediatorParticipant>
<rdf:Description rdf:about="#mediator_3">
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<rdf:Description rdf:about="#entity_12">
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/chebi/CHEBI:64338" />
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<semsim:hasSourceParticipant>
<rdf:Description rdf:about="#source_5" semsim:hasMultiplier="1.0">
<semsim:hasPhysicalEntityReference rdf:resource="#entity_9" />
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</semsim:hasSourceParticipant>
<semsim:name>ATP-sensitive K+ current</semsim:name>
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<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00318" />
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</semsim:isComputationalComponentFor>
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<rdf:Description rdf:about="#membrane.Ikatp">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_4">
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<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00318" />
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<rdf:Description rdf:about="#JF1F0.delta_psi">
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<dcterms:description>Mitochondrial inner membrane potential changes</dcterms:description>
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<rdf:Description rdf:about="#Jmito.JNaCa">
<semsim:isComputationalComponentFor>
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<semsim:physicalPropertyOf rdf:resource="#process_8" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
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<dcterms:description>Calcium flux from mitochondria to the cytosol</dcterms:description>
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<rdf:Description rdf:about="#c.Jmem">
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<rdf:Description rdf:about="#property_91">
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<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
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<dcterms:description>Calcium flux across the plasma membrane.</dcterms:description>
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<rdf:Description rdf:about="#Jer.Jer">
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<semsim:physicalPropertyOf rdf:resource="#process_11" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Flux of calcium out of the endoplasmic reticulun</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cam">
<title xml:lang="en">Cam</title>
<dcterms:alternative xml:lang="en">mitochondrial calcium concentration</dcterms:alternative>
</rdf:Description>
<rdf:Description rdf:about="#Caer">
<title xml:lang="en">Caer</title>
<dcterms:alternative xml:lang="en">calcium</dcterms:alternative>
</rdf:Description>
<rdf:Description rdf:about="#Caer.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#NADHm_NADHm">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_37">
<semsim:physicalPropertyOf rdf:resource="#entity_30" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
</rdf:Description>
<rdf:Description rdf:about="#JF1F0.JF1F0">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_55">
<semsim:physicalPropertyOf rdf:resource="#process_10" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Flux of F1F0 ATP synthase</dcterms:description>
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<rdf:Description rdf:about="#JPDH.NADm">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_33">
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<rdf:Description rdf:about="#delta_psi.JANT">
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</rdf:Description>
<rdf:Description rdf:about="#Ica.Ica">
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<rdf:Description rdf:about="#property_8">
<semsim:physicalPropertyOf rdf:resource="#process_0" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00318" />
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<rdf:Description rdf:about="#F6P">
<title xml:lang="en">F6P</title>
<dcterms:alternative xml:lang="en">fructose 6-phosphate</dcterms:alternative>
</rdf:Description>
<rdf:Description rdf:about="#Ica">
<title xml:lang="en">Ica</title>
<dcterms:alternative xml:lang="en">voltage-dependent calcium current</dcterms:alternative>
</rdf:Description>
<rdf:Description rdf:about="#membrane.Ica">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_1">
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<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00318" />
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</rdf:Description>
<rdf:Description rdf:about="#JO.JO">
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<rdf:Description rdf:about="#property_40">
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<rdf:Description rdf:about="#entity_31">
<ro:part_of rdf:resource="#entity_21" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/chebi/CHEBI:15379" />
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</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Consumption of Oxygen by the mitochondria</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Jleak">
<title xml:lang="en">Jleak</title>
<dcterms:alternative xml:lang="en">rate of calcium leakage out of the endoplasmic reticulum</dcterms:alternative>
</rdf:Description>
<rdf:Description rdf:about="#Jhyd.c">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_85">
<semsim:physicalPropertyOf rdf:resource="#entity_13" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
</rdf:Description>
<rdf:Description rdf:about="#delta_psi.JHres">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_46">
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Flux through respiration-driven proton pumps</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#ADPm">
<title xml:lang="en">ADPm</title>
<dcterms:alternative xml:lang="en">mitochondrial ADP</dcterms:alternative>
</rdf:Description>
<rdf:Description rdf:about="#JHatp.JF1F0">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_59">
<semsim:physicalPropertyOf rdf:resource="#process_10" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
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</semsim:isComputationalComponentFor>
<dcterms:description>Flux of F1F0 ATP synthase</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#c">
<title xml:lang="en">c</title>
<dcterms:alternative xml:lang="en">cytosolic calcium</dcterms:alternative>
</rdf:Description>
<rdf:Description rdf:about="#FBP.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#G6P">
<title xml:lang="en">G6P</title>
<dcterms:alternative xml:lang="en">glucose 6-phosphate</dcterms:alternative>
</rdf:Description>
<rdf:Description rdf:about="#Ikca">
<title xml:lang="en">Ikca</title>
<dcterms:alternative xml:lang="en">calcium-activated potassium current</dcterms:alternative>
</rdf:Description>
<rdf:Description rdf:about="#Jleak.c">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_96">
<semsim:physicalPropertyOf rdf:resource="#entity_13" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
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</rdf:Description>
<rdf:Description rdf:about="#NADm">
<title xml:lang="en">NADm</title>
<dcterms:alternative xml:lang="en">mitochondrial NAD</dcterms:alternative>
</rdf:Description>
<rdf:Description rdf:about="#JGPDH">
<title xml:lang="en">JGPDH</title>
<dcterms:alternative xml:lang="en">rate of the glyceride 3-P dehydrogenase reaction</dcterms:alternative>
</rdf:Description>
<rdf:Description rdf:about="#JNaCa.JNaCa">
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<rdf:Description rdf:about="#property_69">
<semsim:physicalPropertyOf rdf:resource="#process_8" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Calcium flux from mitochondria to the cytosol</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#JPDH.JPDH">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_32">
<semsim:physicalPropertyOf rdf:resource="#process_6" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
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<title xml:lang="en">Ik</title>
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<rdf:Description rdf:about="#ADPm.JANT">
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