Location: Calcium Dynamics Annotations @ 9159ec719051 / deyoung_keizer_1992 / model / deyoung_keizer_1992.cellml

Author:

neilstephen2001 <npar276@aucklanduni.ac.nz>

Date:

2021-01-25 18:26:01+13:00

Desc:

adding OMEX archives to workspace

Permanent Source URI:

http://models.cellml.org/workspace/7f1/rawfile/9159ec71905126c58835aa3923cc1061d893f387/deyoung_keizer_1992/model/deyoung_keizer_1992.cellml

<?xml version="1.0" encoding="UTF-8"?>
<model xmlns="http://www.cellml.org/cellml/1.1#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:semsim="http://www.bhi.washington.edu/SemSim#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" name="deyoung_keizer_1992" cmeta:id="mitochondrial_model_1992">
  <documentation xmlns="http://cellml.org/tmp-documentation">
    <article>
      <articleinfo>
        <title>IP3-Mediated Ca2+ Release</title>
        <author>
          <firstname>Catherine</firstname>
          <surname>Lloyd</surname>
          <affiliation>
            <shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
          </affiliation>
        </author>
      </articleinfo>
      <sect1 id="sec_structure">
        <title>Model Structure</title>
        <para>
          Ca
          <superscript>2+</superscript>
          is a ubiquitous intracellular secondary messenger, and evidence from several different cell types suggests that an important mode of signalling is through oscillations rather than the maintenance of a steady state level.  The oscillatory behaviour of inositol 1,4,5-triphosphate (IP3)-mediated Ca
          <superscript>2+</superscript>
          release has been modelled by Gary W. De Young and Joel Keizer.  Their 1992 paper is referenced fully below.
        </para>
        <para>
          <ulink url="http://www.pnas.org/cgi/content/abstract/89/20/9895">
            A single-pool inositol 1,4,5-triphosphate-receptor-based model for agonist-stimulated oscillations in Ca
            <superscript>2+</superscript>
            concentration
          </ulink>
          , Gary W. De Young and Joel Keizer, 1992,
          <ulink url="http://www.pnas.org/">
            <emphasis>Proc. Natl. Acad. Sci. USA</emphasis>
          </ulink>
          , 89, 9895-9899. (A
          <ulink url="http://www.pnas.org/cgi/reprint/89/20/9895.pdf">PDF</ulink>
          of the article is available to subscribers on the PNAS website.)
          <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;list_uids=1329108&amp;dopt=Abstract">PubMed ID: 1329108</ulink>
        </para>
        <para>
          Several mechanisms have been proposed to explain oscillations of intracellular Ca
          <superscript>2+</superscript>
          concentration in cells.  In this study, De Young and Keizer investigate the idea that a biphasic response of the IP3 receptor/channel to cytosolic Ca
          <superscript>2+</superscript>
          may alone be sufficient to induce Ca
          <superscript>2+</superscript>
          oscillations.
        </para>
        <para>
          They constructed a simplified model of the IP3 receptor/channel by assuming that three equivalent and independent subunits are involved in Ca
          <superscript>2+</superscript>
          conduction.  Each subunit has three binding sites: one for IP3, one for Ca
          <superscript>2+</superscript>
          activation, and one for Ca
          <superscript>2+</superscript>
          inactivation.  Thus each subunit may exist in eight states with transitions governed by second-order (association) and first-order (dissociation) rate constants (see
          <xref linkend="fig_pathway_diagram" />
          below).  All three subunits must be in the state S
          <subscript>110</subscript>
          (one IP3 and one activating Ca
          <superscript>2+</superscript>
          bound) for the channel to be open and conducting.
        </para>
        <para>
          The raw CellML description of the IP3-mediated Ca
          <superscript>2+</superscript>
          release model can be downloaded in various formats as described in
          <xref linkend="sec_download_this_model" />
          .
        </para>
        <informalfigure float="0" id="fig_pathway_diagram">
          <mediaobject>
            <imageobject>
              <objectinfo>
                <title>A schematic diagram of the kinetics of an IP3 receptor/channel subunit</title>
              </objectinfo>
              <imagedata fileref="deyoung_1992.png" />
            </imageobject>
          </mediaobject>
          <caption>
            A schematic diagram of the kinetics of an IP
            <subscript>3</subscript>
            receptor/channel subunit.
          </caption>
        </informalfigure>
      </sect1>
    </article>
  </documentation>
  <units name="first_order_rate_constant">
    <unit exponent="-1.0" units="second" />
  </units>
  <units name="micromolar">
    <unit exponent="-1.0" units="litre" />
    <unit prefix="micro" units="mole" />
  </units>
  <units name="nanomolar">
    <unit prefix="nano" units="mole" />
    <unit exponent="-1.0" units="litre" />
  </units>
  <units name="flux">
    <unit units="micromolar" />
    <unit exponent="-1.0" units="second" />
  </units>
  <units name="second_order_rate_constant">
    <unit exponent="-1.0" units="second" />
    <unit exponent="-1.0" units="micromolar" />
  </units>
  <component name="environment" cmeta:id="submodel_0">
    <variable cmeta:id="environment.time" name="time" public_interface="out" units="second" />
  </component>
  <component name="Ca_i" cmeta:id="Ca_i">
    <variable cmeta:id="Ca_i.Ca_i" name="Ca_i" public_interface="out" units="micromolar" />
    <variable cmeta:id="Ca_i.J1" name="J1" units="flux" />
    <variable cmeta:id="Ca_i.J2" name="J2" units="flux" />
    <variable cmeta:id="Ca_i.v1" initial_value="6.0" name="v1" units="first_order_rate_constant" />
    <variable cmeta:id="Ca_i.v2" initial_value="0.11" name="v2" units="first_order_rate_constant" />
    <variable cmeta:id="Ca_i.v3" initial_value="0.9" name="v3" units="second_order_rate_constant" />
    <variable cmeta:id="Ca_i.k3" initial_value="0.1" name="k3" units="micromolar" />
    <variable cmeta:id="Ca_i.c1" name="c1" public_interface="in" units="dimensionless" />
    <variable cmeta:id="Ca_i.Ca_ER" name="Ca_ER" public_interface="in" units="micromolar" />
    <variable cmeta:id="Ca_i.P_open" name="P_open" public_interface="in" units="dimensionless" />
    <variable cmeta:id="Ca_i.time" name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML" id="1" cmeta:id="1">
      <apply>
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>Ca_i</ci>
        </apply>
        <apply>
          <minus />
          <ci>J1</ci>
          <ci>J2</ci>
        </apply>
      </apply>
      <apply id="J1_calculation">
        <eq />
        <ci>J1</ci>
        <apply>
          <times />
          <ci>c1</ci>
          <apply>
            <plus />
            <apply>
              <times />
              <ci>v1</ci>
              <ci>P_open</ci>
            </apply>
            <ci>v2</ci>
          </apply>
          <apply>
            <minus />
            <ci>Ca_ER</ci>
            <ci>Ca_i</ci>
          </apply>
        </apply>
      </apply>
      <apply id="J2_calculation">
        <eq />
        <ci>J2</ci>
        <apply>
          <divide />
          <apply>
            <times />
            <ci>v3</ci>
            <apply>
              <power />
              <ci>Ca_i</ci>
              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2.0</cn>
            </apply>
          </apply>
          <apply>
            <plus />
            <apply>
              <power />
              <ci>Ca_i</ci>
              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2.0</cn>
            </apply>
            <apply>
              <power />
              <ci>k3</ci>
              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2.0</cn>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  <component name="Ca_ER" cmeta:id="Ca_ER">
    <variable cmeta:id="Ca_ER.Ca_ER" name="Ca_ER" public_interface="out" units="micromolar" />
    <variable cmeta:id="Ca_ER.c0" initial_value="2.0" name="c0" units="micromolar" />
    <variable cmeta:id="Ca_ER.c1" name="c1" public_interface="in" units="dimensionless" />
    <variable cmeta:id="Ca_ER.Ca_i" name="Ca_i" public_interface="in" units="micromolar" />
    <variable cmeta:id="Ca_ER.time" name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML" id="2" cmeta:id="2">
      <apply id="Ca_ER_calculation">
        <eq />
        <ci>Ca_ER</ci>
        <apply>
          <divide />
          <apply>
            <minus />
            <ci>c0</ci>
            <ci>Ca_i</ci>
          </apply>
          <ci>c1</ci>
        </apply>
      </apply>
    </math>
  </component>
  <component name="IP3" cmeta:id="IP3">
    <variable cmeta:id="IP3.IP3" name="IP3" public_interface="out" units="micromolar" />
    <variable cmeta:id="IP3.k4" initial_value="1.1" name="k4" units="micromolar" />
    <variable cmeta:id="IP3.alpha" initial_value="0.5" name="alpha" units="dimensionless" />
    <variable cmeta:id="IP3.Ir" initial_value="1.0" name="Ir" units="flux" />
    <variable cmeta:id="IP3.v4" initial_value="1.2" name="v4" units="first_order_rate_constant" />
    <variable cmeta:id="IP3.Ca_i" name="Ca_i" public_interface="in" units="micromolar" />
    <variable cmeta:id="IP3.time" name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML" id="3" cmeta:id="3">
      <apply>
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>IP3</ci>
        </apply>
        <apply>
          <minus />
          <apply>
            <times />
            <ci>v4</ci>
            <apply>
              <divide />
              <apply>
                <plus />
                <ci>Ca_i</ci>
                <apply>
                  <times />
                  <apply>
                    <minus />
                    <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.0</cn>
                    <ci>alpha</ci>
                  </apply>
                  <ci>k4</ci>
                </apply>
              </apply>
              <apply>
                <plus />
                <ci>Ca_i</ci>
                <ci>k4</ci>
              </apply>
            </apply>
          </apply>
          <apply>
            <times />
            <ci>Ir</ci>
            <ci>IP3</ci>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  <component name="receptor_dissociation_constants" cmeta:id="submodel_1">
    <variable cmeta:id="receptor_dissociation_constants.d1" initial_value="0.13" name="d1" public_interface="out" units="micromolar" />
    <variable cmeta:id="receptor_dissociation_constants.d2" initial_value="1.049" name="d2" public_interface="out" units="micromolar" />
    <variable cmeta:id="receptor_dissociation_constants.d3" initial_value="943.4" name="d3" public_interface="out" units="nanomolar" />
    <variable cmeta:id="receptor_dissociation_constants.d4" name="d4" public_interface="out" units="nanomolar" />
    <variable cmeta:id="receptor_dissociation_constants.d5" initial_value="82.34" name="d5" public_interface="out" units="nanomolar" />
    <variable cmeta:id="receptor_dissociation_constants.a5" name="a5" public_interface="in" units="second_order_rate_constant" />
    <variable cmeta:id="receptor_dissociation_constants.b5" name="b5" public_interface="in" units="first_order_rate_constant" />
    <variable cmeta:id="receptor_dissociation_constants.a2" name="a2" public_interface="in" units="second_order_rate_constant" />
    <variable cmeta:id="receptor_dissociation_constants.b2" name="b2" public_interface="in" units="first_order_rate_constant" />
    <variable cmeta:id="receptor_dissociation_constants.a3" name="a3" public_interface="in" units="second_order_rate_constant" />
    <variable cmeta:id="receptor_dissociation_constants.b3" name="b3" public_interface="in" units="first_order_rate_constant" />
    <variable cmeta:id="receptor_dissociation_constants.a4" name="a4" public_interface="in" units="second_order_rate_constant" />
    <variable cmeta:id="receptor_dissociation_constants.b4" name="b4" public_interface="in" units="first_order_rate_constant" />
    <variable cmeta:id="receptor_dissociation_constants.IP3_cold" initial_value="15.0" name="IP3_cold" units="nanomolar" />
    <variable cmeta:id="receptor_dissociation_constants.K_d2" name="K_d2" units="nanomolar" />
    <variable cmeta:id="receptor_dissociation_constants.K_d1" name="K_d1" units="nanomolar" />
    <math xmlns="http://www.w3.org/1998/Math/MathML" id="5" cmeta:id="5">
      <apply id="d1_calculation">
        <eq />
        <ci>d1</ci>
        <apply>
          <minus />
          <ci>K_d1</ci>
          <ci>IP3_cold</ci>
        </apply>
      </apply>
    </math>
    <math xmlns="http://www.w3.org/1998/Math/MathML" id="5A">
      <apply id="d2_calculation">
        <eq />
        <ci>d2</ci>
        <apply>
          <divide />
          <ci>b2</ci>
          <ci>a2</ci>
        </apply>
      </apply>
    </math>
    <math xmlns="http://www.w3.org/1998/Math/MathML" id="5B">
      <apply id="d3_calculation">
        <eq />
        <ci>d3</ci>
        <apply>
          <minus />
          <apply>
            <times />
            <apply>
              <minus />
              <ci>K_d2</ci>
              <ci>IP3_cold</ci>
            </apply>
            <apply>
              <plus />
              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
              <ci>d2</ci>
            </apply>
          </apply>
          <apply>
            <times />
            <ci>d1</ci>
            <ci>d2</ci>
          </apply>
        </apply>
      </apply>
    </math>
    <math xmlns="http://www.w3.org/1998/Math/MathML" id="5C">
      <apply id="d4_calculation">
        <eq />
        <ci>d4</ci>
        <apply>
          <divide />
          <apply>
            <times />
            <ci>d1</ci>
            <ci>d2</ci>
          </apply>
          <ci>d3</ci>
        </apply>
      </apply>
    </math>
    <math xmlns="http://www.w3.org/1998/Math/MathML" id="5D">
      <apply id="d5_calculation">
        <eq />
        <ci>d5</ci>
        <apply>
          <divide />
          <ci>b5</ci>
          <ci>a5</ci>
        </apply>
      </apply>
    </math>
  </component>
  <component name="probability_of_an_open_IP3_receptor_channel" cmeta:id="probability_of_an_open_IP3_receptor_channel">
    <variable cmeta:id="probability_of_an_open_IP3_receptor_channel.P_open" name="P_open" public_interface="out" units="dimensionless" />
    <variable cmeta:id="probability_of_an_open_IP3_receptor_channel.Ca_i" name="Ca_i" public_interface="in" units="micromolar" />
    <variable cmeta:id="probability_of_an_open_IP3_receptor_channel.IP3" name="IP3" public_interface="in" units="micromolar" />
    <variable cmeta:id="probability_of_an_open_IP3_receptor_channel.d1" name="d1" public_interface="in" units="micromolar" />
    <variable cmeta:id="probability_of_an_open_IP3_receptor_channel.d2" name="d2" public_interface="in" units="micromolar" />
    <variable cmeta:id="probability_of_an_open_IP3_receptor_channel.d3" name="d3" public_interface="in" units="nanomolar" />
    <variable cmeta:id="probability_of_an_open_IP3_receptor_channel.d5" name="d5" public_interface="in" units="nanomolar" />
    <math xmlns="http://www.w3.org/1998/Math/MathML" id="6" cmeta:id="6">
      <apply id="P_open_calculation">
        <eq />
        <ci>P_open</ci>
        <apply>
          <power />
          <apply>
            <divide />
            <apply>
              <times />
              <ci>Ca_i</ci>
              <ci>IP3</ci>
              <ci>d2</ci>
            </apply>
            <apply>
              <times />
              <apply>
                <plus />
                <apply>
                  <times />
                  <ci>Ca_i</ci>
                  <ci>IP3</ci>
                </apply>
                <apply>
                  <times />
                  <ci>IP3</ci>
                  <ci>d2</ci>
                </apply>
                <apply>
                  <times />
                  <ci>d1</ci>
                  <ci>d2</ci>
                </apply>
                <apply>
                  <times />
                  <ci>Ca_i</ci>
                  <ci>d3</ci>
                </apply>
              </apply>
              <apply>
                <plus />
                <ci>Ca_i</ci>
                <ci>d5</ci>
              </apply>
            </apply>
          </apply>
          <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3.0</cn>
        </apply>
      </apply>
    </math>
  </component>
  <component name="x_000" cmeta:id="x_000">
    <variable cmeta:id="x_000.x_000" name="x_000" public_interface="out" units="micromolar" />
    <variable cmeta:id="x_000.V1" name="V1" public_interface="in" units="flux" />
    <variable cmeta:id="x_000.V3" name="V3" public_interface="in" units="flux" />
    <variable cmeta:id="x_000.time" name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML" id="7" cmeta:id="7">
      <apply id="x_000_diff_eq">
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>x_000</ci>
        </apply>
        <apply>
          <minus />
          <apply>
            <minus />
            <ci>V1</ci>
          </apply>
          <ci>V3</ci>
        </apply>
      </apply>
    </math>
  </component>
  <component name="x_001" cmeta:id="x_001">
    <variable cmeta:id="x_001.x_001" name="x_001" public_interface="out" units="micromolar" />
    <variable cmeta:id="x_001.V1" name="V1" public_interface="in" units="flux" />
    <variable cmeta:id="x_001.V4" name="V4" public_interface="in" units="flux" />
    <variable cmeta:id="x_001.time" name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML" id="8" cmeta:id="8">
      <apply id="x_001_diff_eq">
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>x_001</ci>
        </apply>
        <apply>
          <minus />
          <ci>V1</ci>
          <ci>V4</ci>
        </apply>
      </apply>
    </math>
  </component>
  <component name="x_010" cmeta:id="x_010">
    <variable cmeta:id="x_010.x_010" name="x_010" public_interface="out" units="micromolar" />
    <variable cmeta:id="x_010.V2" name="V2" public_interface="in" units="flux" />
    <variable cmeta:id="x_010.V3" name="V3" public_interface="in" units="flux" />
    <variable cmeta:id="x_010.time" name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML" id="9" cmeta:id="9">
      <apply id="x_010_diff_eq">
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>x_010</ci>
        </apply>
        <apply>
          <minus />
          <ci>V3</ci>
          <ci>V2</ci>
        </apply>
      </apply>
    </math>
  </component>
  <component name="x_011" cmeta:id="x_011">
    <variable cmeta:id="x_011.x_011" name="x_011" public_interface="out" units="micromolar" />
    <variable cmeta:id="x_011.x_000" name="x_000" public_interface="in" units="micromolar" />
    <variable cmeta:id="x_011.x_001" name="x_001" public_interface="in" units="micromolar" />
    <variable cmeta:id="x_011.x_010" name="x_010" public_interface="in" units="micromolar" />
    <math xmlns="http://www.w3.org/1998/Math/MathML" id="8a" cmeta:id="8a">
      <apply id="x_011_eq">
        <eq />
        <ci>x_011</ci>
        <apply>
          <minus />
          <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.0</cn>
          <apply>
            <plus />
            <ci>x_000</ci>
            <ci>x_001</ci>
            <ci>x_010</ci>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  <component name="fluxes" cmeta:id="submodel_2">
    <variable cmeta:id="fluxes.V1" name="V1" public_interface="out" units="flux" />
    <variable cmeta:id="fluxes.V2" name="V2" public_interface="out" units="flux" />
    <variable cmeta:id="fluxes.V3" name="V3" public_interface="out" units="flux" />
    <variable cmeta:id="fluxes.V4" name="V4" public_interface="out" units="flux" />
    <variable cmeta:id="fluxes.x_000" name="x_000" public_interface="in" units="micromolar" />
    <variable cmeta:id="fluxes.x_001" name="x_001" public_interface="in" units="micromolar" />
    <variable cmeta:id="fluxes.x_011" name="x_011" public_interface="in" units="micromolar" />
    <variable cmeta:id="fluxes.x_010" name="x_010" public_interface="in" units="micromolar" />
    <variable cmeta:id="fluxes.Ca_i" name="Ca_i" public_interface="in" units="micromolar" />
    <variable cmeta:id="fluxes.a4" name="a4" public_interface="in" units="second_order_rate_constant" />
    <variable cmeta:id="fluxes.d4" name="d4" public_interface="in" units="nanomolar" />
    <variable cmeta:id="fluxes.a5" name="a5" public_interface="in" units="second_order_rate_constant" />
    <variable cmeta:id="fluxes.d5" name="d5" public_interface="in" units="nanomolar" />
    <variable cmeta:id="fluxes.time" name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML" id="10" cmeta:id="10">
      <apply id="V1_calculation">
        <eq />
        <ci>V1</ci>
        <apply>
          <times />
          <ci>a4</ci>
          <apply>
            <minus />
            <apply>
              <times />
              <ci>Ca_i</ci>
              <ci>x_000</ci>
            </apply>
            <apply>
              <times />
              <ci>d4</ci>
              <ci>x_001</ci>
            </apply>
          </apply>
        </apply>
      </apply>
      <apply id="V2_calculation">
        <eq />
        <ci>V2</ci>
        <apply>
          <times />
          <ci>a4</ci>
          <apply>
            <minus />
            <apply>
              <times />
              <ci>Ca_i</ci>
              <ci>x_010</ci>
            </apply>
            <apply>
              <times />
              <ci>d4</ci>
              <ci>x_011</ci>
            </apply>
          </apply>
        </apply>
      </apply>
      <apply id="V3_calculation">
        <eq />
        <ci>V3</ci>
        <apply>
          <times />
          <ci>a5</ci>
          <apply>
            <minus />
            <apply>
              <times />
              <ci>Ca_i</ci>
              <ci>x_000</ci>
            </apply>
            <apply>
              <times />
              <ci>d5</ci>
              <ci>x_010</ci>
            </apply>
          </apply>
        </apply>
      </apply>
      <apply id="V4_calculation">
        <eq />
        <ci>V4</ci>
        <apply>
          <times />
          <ci>a5</ci>
          <apply>
            <minus />
            <apply>
              <times />
              <ci>Ca_i</ci>
              <ci>x_001</ci>
            </apply>
            <apply>
              <times />
              <ci>d5</ci>
              <ci>x_011</ci>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  <component name="constants" cmeta:id="submodel_3">
    <variable cmeta:id="constants.a1" initial_value="400.0" name="a1" public_interface="out" units="second_order_rate_constant" />
    <variable cmeta:id="constants.b1" name="b1" public_interface="out" units="first_order_rate_constant" />
    <variable cmeta:id="constants.a2" initial_value="0.2" name="a2" public_interface="out" units="second_order_rate_constant" />
    <variable cmeta:id="constants.b2" name="b2" public_interface="out" units="first_order_rate_constant" />
    <variable cmeta:id="constants.a3" initial_value="400.0" name="a3" public_interface="out" units="second_order_rate_constant" />
    <variable cmeta:id="constants.b3" name="b3" public_interface="out" units="first_order_rate_constant" />
    <variable cmeta:id="constants.a4" initial_value="0.2" name="a4" public_interface="out" units="second_order_rate_constant" />
    <variable cmeta:id="constants.b4" name="b4" public_interface="out" units="first_order_rate_constant" />
    <variable cmeta:id="constants.a5" initial_value="20.0" name="a5" public_interface="out" units="second_order_rate_constant" />
    <variable cmeta:id="constants.b5" name="b5" public_interface="out" units="first_order_rate_constant" />
    <variable cmeta:id="constants.c1" initial_value="0.185" name="c1" public_interface="out" units="dimensionless" />
    <variable cmeta:id="constants.d1" name="d1" public_interface="in" units="micromolar" />
    <variable cmeta:id="constants.d3" name="d3" public_interface="in" units="nanomolar" />
    <variable cmeta:id="constants.d4" name="d4" public_interface="in" units="nanomolar" />
    <math xmlns="http://www.w3.org/1998/Math/MathML" id="11" cmeta:id="11">
      <apply id="b1_calculation">
        <eq />
        <ci>b1</ci>
        <apply>
          <times />
          <ci>d1</ci>
          <ci>a1</ci>
        </apply>
      </apply>
      <apply id="b3_calculation">
        <eq />
        <ci>b3</ci>
        <apply>
          <times />
          <ci>d3</ci>
          <ci>a3</ci>
        </apply>
      </apply>
      <apply id="b4_calculation">
        <eq />
        <ci>b4</ci>
        <apply>
          <times />
          <ci>d4</ci>
          <ci>a4</ci>
        </apply>
      </apply>
    </math>
  </component>
  <connection>
    <map_components component_1="x_000" component_2="fluxes" />
    <map_variables variable_1="x_000" variable_2="x_000" />
  </connection>
  <connection>
    <map_components component_1="environment" component_2="Ca_ER" />
    <map_variables variable_1="time" variable_2="time" />
  </connection>
  <connection>
    <map_components component_1="Ca_ER" component_2="Ca_i" />
    <map_variables variable_1="Ca_ER" variable_2="Ca_ER" />
  </connection>
  <connection>
    <map_components component_1="x_010" component_2="x_011" />
    <map_variables variable_1="x_010" variable_2="x_010" />
  </connection>
  <connection>
    <map_components component_1="fluxes" component_2="x_000" />
    <map_variables variable_1="V3" variable_2="V3" />
    <map_variables variable_1="V1" variable_2="V1" />
  </connection>
  <connection>
    <map_components component_1="x_010" component_2="fluxes" />
    <map_variables variable_1="x_010" variable_2="x_010" />
  </connection>
  <connection>
    <map_components component_1="constants" component_2="fluxes" />
    <map_variables variable_1="a5" variable_2="a5" />
    <map_variables variable_1="a4" variable_2="a4" />
  </connection>
  <connection>
    <map_components component_1="environment" component_2="fluxes" />
    <map_variables variable_1="time" variable_2="time" />
  </connection>
  <connection>
    <map_components component_1="IP3" component_2="probability_of_an_open_IP3_receptor_channel" />
    <map_variables variable_1="IP3" variable_2="IP3" />
  </connection>
  <connection>
    <map_components component_1="fluxes" component_2="x_001" />
    <map_variables variable_1="V1" variable_2="V1" />
    <map_variables variable_1="V4" variable_2="V4" />
  </connection>
  <connection>
    <map_components component_1="environment" component_2="x_000" />
    <map_variables variable_1="time" variable_2="time" />
  </connection>
  <connection>
    <map_components component_1="environment" component_2="x_010" />
    <map_variables variable_1="time" variable_2="time" />
  </connection>
  <connection>
    <map_components component_1="receptor_dissociation_constants" component_2="probability_of_an_open_IP3_receptor_channel" />
    <map_variables variable_1="d5" variable_2="d5" />
    <map_variables variable_1="d3" variable_2="d3" />
    <map_variables variable_1="d2" variable_2="d2" />
    <map_variables variable_1="d1" variable_2="d1" />
  </connection>
  <connection>
    <map_components component_1="environment" component_2="x_001" />
    <map_variables variable_1="time" variable_2="time" />
  </connection>
  <connection>
    <map_components component_1="environment" component_2="Ca_i" />
    <map_variables variable_1="time" variable_2="time" />
  </connection>
  <connection>
    <map_components component_1="Ca_i" component_2="IP3" />
    <map_variables variable_1="Ca_i" variable_2="Ca_i" />
  </connection>
  <connection>
    <map_components component_1="x_000" component_2="x_011" />
    <map_variables variable_1="x_000" variable_2="x_000" />
  </connection>
  <connection>
    <map_components component_1="receptor_dissociation_constants" component_2="fluxes" />
    <map_variables variable_1="d5" variable_2="d5" />
    <map_variables variable_1="d4" variable_2="d4" />
  </connection>
  <connection>
    <map_components component_1="constants" component_2="Ca_ER" />
    <map_variables variable_1="c1" variable_2="c1" />
  </connection>
  <connection>
    <map_components component_1="constants" component_2="Ca_i" />
    <map_variables variable_1="c1" variable_2="c1" />
  </connection>
  <connection>
    <map_components component_1="Ca_i" component_2="Ca_ER" />
    <map_variables variable_1="Ca_i" variable_2="Ca_i" />
  </connection>
  <connection>
    <map_components component_1="x_011" component_2="fluxes" />
    <map_variables variable_1="x_011" variable_2="x_011" />
  </connection>
  <connection>
    <map_components component_1="x_001" component_2="fluxes" />
    <map_variables variable_1="x_001" variable_2="x_001" />
  </connection>
  <connection>
    <map_components component_1="fluxes" component_2="x_010" />
    <map_variables variable_1="V3" variable_2="V3" />
    <map_variables variable_1="V2" variable_2="V2" />
  </connection>
  <connection>
    <map_components component_1="constants" component_2="receptor_dissociation_constants" />
    <map_variables variable_1="b4" variable_2="b4" />
    <map_variables variable_1="b2" variable_2="b2" />
    <map_variables variable_1="b3" variable_2="b3" />
    <map_variables variable_1="a5" variable_2="a5" />
    <map_variables variable_1="a2" variable_2="a2" />
    <map_variables variable_1="a3" variable_2="a3" />
    <map_variables variable_1="a4" variable_2="a4" />
    <map_variables variable_1="b5" variable_2="b5" />
  </connection>
  <connection>
    <map_components component_1="receptor_dissociation_constants" component_2="constants" />
    <map_variables variable_1="d3" variable_2="d3" />
    <map_variables variable_1="d4" variable_2="d4" />
    <map_variables variable_1="d1" variable_2="d1" />
  </connection>
  <connection>
    <map_components component_1="environment" component_2="IP3" />
    <map_variables variable_1="time" variable_2="time" />
  </connection>
  <connection>
    <map_components component_1="Ca_i" component_2="probability_of_an_open_IP3_receptor_channel" />
    <map_variables variable_1="Ca_i" variable_2="Ca_i" />
  </connection>
  <connection>
    <map_components component_1="x_001" component_2="x_011" />
    <map_variables variable_1="x_001" variable_2="x_001" />
  </connection>
  <connection>
    <map_components component_1="probability_of_an_open_IP3_receptor_channel" component_2="Ca_i" />
    <map_variables variable_1="P_open" variable_2="P_open" />
  </connection>
  <connection>
    <map_components component_1="Ca_i" component_2="fluxes" />
    <map_variables variable_1="Ca_i" variable_2="Ca_i" />
  </connection>
  <rdf:RDF xmlns:bqmodel="http://biomodels.net/model-qualifiers/" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:ro="http://www.obofoundry.org/ro/ro.owl#" xmlns:opb="http://bhi.washington.edu/OPB#">
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#receptor_dissociation_constants.d4">
      <bqbiol:isPropertyOf>
        <rdf:Description rdf:about="deyoung_keizer_1992.cellml#entity_2">
          <bqbiol:is rdf:resource="http://identifiers.org/fma/FMA:66835" />
        </rdf:Description>
      </bqbiol:isPropertyOf>
      <dcterms:description>calcium inhibition receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#x_000.V1">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_26">
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>rate of conversion from IP3 receptor subunit state 000 to state 001</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#x_010.V2">
      <dcterms:description>rate of conversion from IP3 receptor subunit state 010 to state 011</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#receptor_dissociation_constants.d1">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_11">
          <semsim:physicalPropertyOf>
            <rdf:Description rdf:about="#entity_0">
              <ro:part_of>
                <rdf:Description rdf:about="#entity_1">
                  <semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/go/GO:0005829" />
                </rdf:Description>
              </ro:part_of>
              <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/chebi/CHEBI:29108" />
            </rdf:Description>
          </semsim:physicalPropertyOf>
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>IP3 receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#x_011.x_001">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_36">
          <semsim:physicalPropertyOf>
            <rdf:Description rdf:about="#entity_7">
              <ro:part_of rdf:resource="#entity_1" />
              <semsim:hasPhysicalDefinition rdf:resource="http://purl.obolibrary.org/obo/PR_Q9Y6F6" />
            </rdf:Description>
          </semsim:physicalPropertyOf>
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of IP3 receptor subunit state 001 with free calcium activation site and occupied calcium inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#probability_of_an_open_IP3_receptor_channel.d5">
      <bqbiol:isPropertyOf>
        <rdf:Description rdf:about="deyoung_keizer_1992.cellml#entity_0">
          <bqbiol:is rdf:resource="http://identifiers.org/go/GO:0005829" />
        </rdf:Description>
      </bqbiol:isPropertyOf>
      <dcterms:description>calcium activation receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#constants.b1">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>IP3 receptor binding constant multiplied by receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#constants.a3">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>IP3 receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#constants.b5">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium activation receptor binding constant multiplied by receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#Ca_ER.time">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#fluxes.d4">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>calcium inhibition receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#fluxes.x_001">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>concentration of IP3 receptor subunit state 001 with free calcium activation site and occupied calcium inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#fluxes.d5">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_48">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>calcium activation receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#IP3.v4">
      <dcterms:description>maximum rate of IP3 production</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#Ca_ER.Ca_i">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_7">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of free cytosolic calcium</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#x_010.V3">
      <dcterms:description>rate of conversion from IP3 receptor subunit state 000 to state 010</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#x_001.time">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
    </rdf:Description>
    <rdf:Description rdf:about="#x_011.x_000">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_35">
          <semsim:physicalPropertyOf rdf:resource="#entity_7" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of IP3 receptor subunit state 000 with free calcium activation site and free calcium inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#constants.b2">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium inhibition receptor binding constant multiplied by receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#receptor_dissociation_constants.d3">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>IP3 receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#x_000.x_000">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_25">
          <semsim:physicalPropertyOf rdf:resource="#entity_7" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of IP3 receptor subunit state 000 with free calcium activation site and free calcium inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#Ca_ER.c1">
      <dcterms:description>ratio of endoplasmic reticulum volume to cytosolic volume</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#constants.b4">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium inhibition receptor binding constant multiplied by receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#constants.a2">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium inhibition receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#Ca_ER.Ca_ER">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_5">
          <semsim:physicalPropertyOf>
            <rdf:Description rdf:about="#entity_2">
              <ro:part_of>
                <rdf:Description rdf:about="#entity_3">
                  <semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/fma/FMA:63842" />
                </rdf:Description>
              </ro:part_of>
              <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/chebi/CHEBI:29108" />
            </rdf:Description>
          </semsim:physicalPropertyOf>
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of calcium in endoplasmic reticulum</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#probability_of_an_open_IP3_receptor_channel.P_open">
      <dcterms:description>probability of an open IP3 receptor at equilibrium</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#Ca_i.c1">
      <dcterms:description>ratio of endoplasmic reticulum volume to cytosolic volume</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#Ca_i.Ca_i">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_0">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of free cytosolic calcium</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#mitochondrial_model_1992" bqmodel:isDescribedBy="1329108" />
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#fluxes.d5">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_0" />
      <dcterms:description>calcium activation receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#fluxes.x_000">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>concentration of IP3 receptor subunit state 000 with free calcium activation site and free calcium inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#receptor_dissociation_constants.b2">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium inhibition receptor binding constant multiplied by receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#constants.c1">
      <dcterms:description>ratio of endoplasmic reticulum volume to cytosolic volume</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#probability_of_an_open_IP3_receptor_channel.Ca_i">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_0" />
      <dcterms:description>concentration of free cytosolic calcium</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#x_011.x_011">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_34">
          <semsim:physicalPropertyOf rdf:resource="#entity_7" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of IP3 receptor subunit state 011 with occupied calcium activation site and free occupied inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#constants.d3">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>IP3 receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#Ca_i.time">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
    </rdf:Description>
    <rdf:Description rdf:about="#constants.a1">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>IP3 receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#x_010.x_010">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>concentration of IP3 receptor subunit state 010 with occupied calcium activation site and free calcium inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#constants.b3">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>IP3 receptor binding constant multiplied by receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#probability_of_an_open_IP3_receptor_channel.d3">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>IP3 receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#x_000.x_000">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>concentration of IP3 receptor subunit state 000 with free calcium activation site and free calcium inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#Ca_ER.c0">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>total intracellular calcium in terms of cytosolic volume</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#Ca_i.J1">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_1">
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>outward flux of calcium from the IP3-sensitive calcium pool into the cytosol</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#fluxes.x_011">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>concentration of IP3 receptor subunit state 011 with occupied calcium activation site and free occupied inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#x_011.x_010">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_37">
          <semsim:physicalPropertyOf rdf:resource="#entity_7" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of IP3 receptor subunit state 010 with occupied calcium activation site and free calcium inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#probability_of_an_open_IP3_receptor_channel.P_open">
      <dcterms:description>probability of an open IP3 receptor at equilibrium</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#Ca_i.c1">
      <dcterms:description>ratio of endoplasmic reticulum volume to cytosolic volume</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#Ca_i.Ca_ER">
      <bqbiol:isPropertyOf>
        <rdf:Description rdf:about="deyoung_keizer_1992.cellml#entity_1">
          <bqbiol:is rdf:resource="http://identifiers.org/fma/FMA:63842" />
        </rdf:Description>
      </bqbiol:isPropertyOf>
      <dcterms:description>concentration of calcium in endoplasmic reticulum</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#receptor_dissociation_constants.d5">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_0" />
      <dcterms:description>calcium activation receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#IP3.v4">
      <dcterms:description>maximum rate of IP3 production</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#fluxes.x_010">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>concentration of IP3 receptor subunit state 010 with occupied calcium activation site and free calcium inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#Ca_i.J1">
      <dcterms:description>outward flux of calcium from the IP3-sensitive calcium pool into the cytosol</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#constants.d4">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>calcium inhibition receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#constants.b2">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium inhibition receptor binding constant multiplied by receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#x_011.x_001">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>concentration of IP3 receptor subunit state 001 with free calcium activation site and occupied calcium inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#Ca_ER.Ca_i">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_0" />
      <dcterms:description>concentration of free cytosolic calcium</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#Ca_i.J2">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_2">
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>inward flux of calcium from the cytosol into the IP3-sensitive calcium pool</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#Ca_i.k3">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_3">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>activation constant for calcium ATPase pump</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#x_010.time">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#receptor_dissociation_constants.a2">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium inhibition receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#receptor_dissociation_constants.b4">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium inhibition receptor binding constant multiplied by receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#Ca_i.v1">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>maximum calcium channel flux</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#fluxes.V4">
      <dcterms:description>rate of conversion from IP3 receptor subunit state 001 to state 011</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#Ca_i.J2">
      <dcterms:description>inward flux of calcium from the cytosol into the IP3-sensitive calcium pool</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#Ca_i.k3">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_0" />
      <dcterms:description>activation constant for calcium ATPase pump</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#constants.a3">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>IP3 receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#receptor_dissociation_constants.IP3_cold">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>concentration of IP3 used in the cold titration process</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#constants.b1">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>IP3 receptor binding constant multiplied by receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#probability_of_an_open_IP3_receptor_channel.d1">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>IP3 receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#fluxes.V4">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_41">
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>rate of conversion from IP3 receptor subunit state 001 to state 011</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#x_001.V1">
      <dcterms:description>rate of conversion from IP3 receptor subunit state 000 to state 001</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#fluxes.time">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#constants.b5">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium activation receptor binding constant multiplied by receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#Ca_i.v2">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium leak flux constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#receptor_dissociation_constants.b3">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>IP3 receptor binding constant multiplied by receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#mitochondrial_model_1992" semsim:modelName="deyoung_keizer_1992" bqmodel:isDescribedBy="1329108">
      <semsim:unknown>IP3 Receptor</semsim:unknown>
      <semsim:modelName>deyoung_keizer_1992_version01</semsim:modelName>
      <semsim:unknown>The De Young-Keizer 1992 model of oscillatory calcium release through
        the IP3 stimulated channel</semsim:unknown>
    </rdf:Description>
    <rdf:Description rdf:about="#constants.d4">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_51">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>calcium inhibition receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#probability_of_an_open_IP3_receptor_channel.d2">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_0" />
      <dcterms:description>calcium inhibition receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#IP3.alpha">
      <dcterms:description>calcium stimulation factor of IP3 production</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#fluxes.V3">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_40">
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>rate of conversion from IP3 receptor subunit state 000 to state 010</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#Ca_i.P_open">
      <dcterms:description>probability of an open IP3 receptor at equilibrium</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#fluxes.a4">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium inhibition receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#receptor_dissociation_constants.K_d1">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>effective dissociation constant for IP3 binding to microsomal endoplasmic reticulum when calcium is absent</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#constants.a4">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium inhibition receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#IP3.time">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
    </rdf:Description>
    <rdf:Description rdf:about="#environment.time">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
    </rdf:Description>
    <rdf:Description rdf:about="#Ca_i.v3">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>maximum calcium uptake</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#receptor_dissociation_constants.a4">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium inhibition receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#constants.b3">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>IP3 receptor binding constant multiplied by receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#Ca_i.Ca_i">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_0" />
      <dcterms:description>concentration of free cytosolic calcium</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#constants.a1">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>IP3 receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#x_000.V3">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_27">
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>rate of conversion from IP3 receptor subunit state 000 to state 010</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#constants.d3">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_50">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>IP3 receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#Ca_i.time">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
    </rdf:Description>
    <rdf:Description rdf:about="#receptor_dissociation_constants.a5">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium activation receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#fluxes.V2">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_39">
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>rate of conversion from IP3 receptor subunit state 010 to state 011</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#x_001.V4">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_30">
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>rate of conversion from IP3 receptor subunit state 001 to state 011</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#constants.c1">
      <dcterms:description>ratio of endoplasmic reticulum volume to cytosolic volume</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#fluxes.a5">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium activation receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#receptor_dissociation_constants.K_d2">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>effective dissociation constant for IP3 binding to microsomal endoplasmic reticulum when 1 micromolar calcium is present</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#Ca_i.P_open">
      <dcterms:description>probability of an open IP3 receptor at equilibrium</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#IP3.IP3">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>concentration of IP3</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#Ca_ER.c0">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_6">
          <semsim:physicalPropertyOf>
            <rdf:Description rdf:about="#entity_4">
              <semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/fma/FMA:66835" />
            </rdf:Description>
          </semsim:physicalPropertyOf>
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>total intracellular calcium in terms of cytosolic volume</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#receptor_dissociation_constants.a3">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>IP3 receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#Ca_ER.c1">
      <dcterms:description>ratio of endoplasmic reticulum volume to cytosolic volume</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#receptor_dissociation_constants.b5">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium activation receptor binding constant multiplied by receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#constants.a2">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium inhibition receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#constants.b4">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium inhibition receptor binding constant multiplied by receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#receptor_dissociation_constants.a4">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium inhibition receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#probability_of_an_open_IP3_receptor_channel.IP3">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>concentration of IP3</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#fluxes.V1">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_38">
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>rate of conversion from IP3 receptor subunit state 000 to state 001</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#IP3.Ca_i">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_10">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of free cytosolic calcium</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#x_000.V1">
      <dcterms:description>rate of conversion from IP3 receptor subunit state 000 to state 001</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#receptor_dissociation_constants.b5">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium activation receptor binding constant multiplied by receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#x_010.V2">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_32">
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>rate of conversion from IP3 receptor subunit state 010 to state 011</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#receptor_dissociation_constants.a3">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>IP3 receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#fluxes.Ca_i">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_46">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of free cytosolic calcium</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#constants.d1">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_49">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>IP3 receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#probability_of_an_open_IP3_receptor_channel.d2">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_22">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>calcium inhibition receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#fluxes.V1">
      <dcterms:description>rate of conversion from IP3 receptor subunit state 000 to state 001</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#fluxes.x_010">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_45">
          <semsim:physicalPropertyOf rdf:resource="#entity_7" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of IP3 receptor subunit state 010 with occupied calcium activation site and free calcium inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#receptor_dissociation_constants.a2">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium inhibition receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#receptor_dissociation_constants.b4">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium inhibition receptor binding constant multiplied by receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#x_001.x_001">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>concentration of IP3 receptor subunit state 001 with free calcium activation site and occupied calcium inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#receptor_dissociation_constants.a5">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium activation receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#fluxes.time">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#x_000.time">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
    </rdf:Description>
    <rdf:Description rdf:about="#probability_of_an_open_IP3_receptor_channel.d3">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_23">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>IP3 receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#fluxes.V2">
      <dcterms:description>rate of conversion from IP3 receptor subunit state 010 to state 011</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#fluxes.x_011">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_44">
          <semsim:physicalPropertyOf rdf:resource="#entity_7" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of IP3 receptor subunit state 011 with occupied calcium activation site and free occupied inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#receptor_dissociation_constants.b3">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>IP3 receptor binding constant multiplied by receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#x_001.V4">
      <dcterms:description>rate of conversion from IP3 receptor subunit state 001 to state 011</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#x_001.x_001">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_28">
          <semsim:physicalPropertyOf rdf:resource="#entity_7" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of IP3 receptor subunit state 001 with free calcium activation site and occupied calcium inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#IP3.IP3">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_8">
          <semsim:physicalPropertyOf>
            <rdf:Description rdf:about="#entity_5">
              <ro:part_of rdf:resource="#entity_1" />
              <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/chebi/CHEBI:16595" />
            </rdf:Description>
          </semsim:physicalPropertyOf>
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of IP3</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#IP3.time">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#constants.a5">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium activation receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#receptor_dissociation_constants.IP3_cold">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_16">
          <semsim:physicalPropertyOf>
            <rdf:Description rdf:about="#entity_6">
              <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/chebi/CHEBI:16595" />
            </rdf:Description>
          </semsim:physicalPropertyOf>
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of IP3 used in the cold titration process</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#fluxes.x_000">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_42">
          <semsim:physicalPropertyOf rdf:resource="#entity_7" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of IP3 receptor subunit state 000 with free calcium activation site and free calcium inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#fluxes.V3">
      <dcterms:description>rate of conversion from IP3 receptor subunit state 000 to state 010</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#receptor_dissociation_constants.b2">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium inhibition receptor binding constant multiplied by receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#x_010.V3">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_33">
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>rate of conversion from IP3 receptor subunit state 000 to state 010</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#fluxes.Ca_i">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_0" />
      <dcterms:description>concentration of free cytosolic calcium</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#x_001.V1">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_29">
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00593" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>rate of conversion from IP3 receptor subunit state 000 to state 001</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#probability_of_an_open_IP3_receptor_channel.d5">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_24">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>calcium activation receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#IP3.alpha">
      <dcterms:description>calcium stimulation factor of IP3 production</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#probability_of_an_open_IP3_receptor_channel.IP3">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_20">
          <semsim:physicalPropertyOf rdf:resource="#entity_5" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of IP3</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#x_010.time">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#constants.d1">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>IP3 receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#x_000.time">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
    </rdf:Description>
    <rdf:Description rdf:about="#fluxes.x_001">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_43">
          <semsim:physicalPropertyOf rdf:resource="#entity_7" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of IP3 receptor subunit state 001 with free calcium activation site and occupied calcium inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#receptor_dissociation_constants.K_d1">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_18">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>effective dissociation constant for IP3 binding to microsomal endoplasmic reticulum when calcium is absent</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#receptor_dissociation_constants.d5">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_15">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>calcium activation receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#IP3.Ir">
      <dcterms:description>rate constant for loss of IP3</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#x_001.time">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
    </rdf:Description>
    <rdf:Description rdf:about="#IP3.Ir">
      <dcterms:description>rate constant for loss of IP3</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#Ca_i.v1">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>maximum calcium channel flux</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#x_011.x_000">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>concentration of IP3 receptor subunit state 000 with free calcium activation site and free calcium inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#probability_of_an_open_IP3_receptor_channel.Ca_i">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_19">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of free cytosolic calcium</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#Ca_i.Ca_ER">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_4">
          <semsim:physicalPropertyOf rdf:resource="#entity_2" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of calcium in endoplasmic reticulum</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#IP3.Ca_i">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_0" />
      <dcterms:description>concentration of free cytosolic calcium</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#receptor_dissociation_constants.K_d2">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_17">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>effective dissociation constant for IP3 binding to microsomal endoplasmic reticulum when 1 micromolar calcium is present</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#Ca_i.v2">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium leak flux constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#receptor_dissociation_constants.d4">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_14">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>calcium inhibition receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#IP3.k4">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_9">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>dissociation constant for calcium stimulation of IP3 production</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#x_011.x_011">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>concentration of IP3 receptor subunit state 011 with occupied calcium activation site and free occupied inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#environment.time">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#Ca_ER.Ca_ER">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_1" />
      <dcterms:description>concentration of calcium in endoplasmic reticulum</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#receptor_dissociation_constants.d3">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_13">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>IP3 receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#receptor_dissociation_constants.d2">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_0" />
      <dcterms:description>calcium inhibition receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#Ca_i.v3">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>maximum calcium uptake</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#x_011.x_010">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>concentration of IP3 receptor subunit state 010 with occupied calcium activation site and free calcium inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#constants.a5">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium activation receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#fluxes.a4">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium inhibition receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#x_010.x_010">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_31">
          <semsim:physicalPropertyOf rdf:resource="#entity_7" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>concentration of IP3 receptor subunit state 010 with occupied calcium activation site and free calcium inactivation site</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#receptor_dissociation_constants.d1">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_2" />
      <dcterms:description>IP3 receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#receptor_dissociation_constants.d2">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_12">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>calcium inhibition receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#IP3.k4">
      <bqbiol:isPropertyOf rdf:resource="deyoung_keizer_1992.cellml#entity_0" />
      <dcterms:description>dissociation constant for calcium stimulation of IP3 production</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#constants.a4">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium inhibition receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#x_000.V3">
      <dcterms:description>rate of conversion from IP3 receptor subunit state 000 to state 010</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#fluxes.a5">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
      <dcterms:description>calcium activation receptor binding constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#probability_of_an_open_IP3_receptor_channel.d1">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_21">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>IP3 receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="#fluxes.d4">
      <semsim:isComputationalComponentFor>
        <rdf:Description rdf:about="#property_47">
          <semsim:physicalPropertyOf rdf:resource="#entity_0" />
          <semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
        </rdf:Description>
      </semsim:isComputationalComponentFor>
      <dcterms:description>calcium inhibition receptor dissociation constant</dcterms:description>
    </rdf:Description>
    <rdf:Description rdf:about="deyoung_keizer_1992.cellml#Ca_ER.time">
      <bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
    </rdf:Description>
  </rdf:RDF>
</model>