Location: A Bifurcation Analysis of Two Coupled Calcium Oscillators, Bindschadler and Sneyd 2001 @ 9d7550217f6b / model / bindschadler_sneyd_2001.cellml

Author:
AnandR <a.rampadarath@auckland.ac.nz>
Date:
2019-09-11 15:23:10+12:00
Desc:
added .omex files.
Permanent Source URI:
https://models.fieldml.org/workspace/597/rawfile/9d7550217f6b6a7533a82f10bf8b455a2987089f/model/bindschadler_sneyd_2001.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="bindschadler_sneyd_2001" cmeta:id="bindschadler_sneyd_2001">
  <documentation xmlns="http://cellml.org/tmp-documentation">
    <article>
      <articleinfo>
        <title>A Bifurcation Analysis of Two Coupled Calcium Oscillators</title>
        <author>
          <firstname>Catherine</firstname>
          <surname>Lloyd</surname>
          <affiliation>
            <shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
          </affiliation>
        </author>
      </articleinfo>
      <section id="sec_status">
        <title>Model Status</title>
        <para>This CellML model runs in both OpenCell and COR to produce an oscillating output similar to that from the original published model. The units have been checked and they are consistent.</para>
      </section>
      <sect1 id="sec_structure">
        <title>Model Structure</title>
        <para>ABSTRACT: In many cell types, asynchronous or synchronous oscillations in the concentration of intracellular free calcium occur in adjacent cells that are coupled by gap junctions. Such oscillations are believed to underlie oscillatory intercellular calcium waves in some cell types, and thus it is important to understand how they occur and are modified by intercellular coupling. Using a previous model of intracellular calcium oscillations in pancreatic acinar cells, this article explores the effects of coupling two cells with a simple linear diffusion term. Depending on the concentration of a signal molecule, inositol (1,4,5)-trisphosphate, coupling two identical cells by diffusion can give rise to synchronized in-phase oscillations, as well as different-amplitude in-phase oscillations and same-amplitude antiphase oscillations. Coupling two nonidentical cells leads to more complex behaviors such as cascades of period doubling and multiply periodic solutions. This study is a first step towards understanding the role and significance of the diffusion of calcium through gap junctions in the coordination of oscillatory calcium waves in a variety of cell types.</para>
        <para>The original paper reference is cited below:</para>
        <para>
          A bifurcation analysis of two coupled calcium oscillators, Michael Bindschadler and James Sneyd, 2001,
          <emphasis>CHAOS</emphasis>
          , 11, 237-246.
          <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/12779457">PubMed ID: 12779457</ulink>
        </para>
        <informalfigure float="0" id="fig_cell_diagram">
          <mediaobject>
            <imageobject>
              <objectinfo>
                <title>cell diagram</title>
              </objectinfo>
              <imagedata fileref="bindschadler_2001.png" />
            </imageobject>
            <caption>Schematic diagram of the IP3 receptor model.  The receptor with its three possible states: X, Y, and Z; representing open, shut and inactive respectively, is embedded within a model of intracellular calcium dynamics.</caption>
          </mediaobject>
        </informalfigure>
      </sect1>
    </article>
  </documentation>
  <units name="per_second">
    <unit exponent="-1.0" units="second" />
  </units>
  <units name="second_order_rate">
    <unit exponent="-1.0" units="micro_molar" />
    <unit units="per_second" />
  </units>
  <units name="micro_molar">
    <unit prefix="micro" units="mole" />
    <unit exponent="-1.0" units="litre" />
  </units>
  <units name="micro_molar_per_second">
    <unit units="per_second" />
    <unit units="micro_molar" />
  </units>
  <component name="h2">
    <variable cmeta:id="h2.p" name="p" public_interface="in" units="micro_molar" />
    <variable cmeta:id="h2.time" name="time" public_interface="in" units="second" />
    <variable cmeta:id="h2.phi1_c2" name="phi1_c2" public_interface="in" units="second_order_rate" />
    <variable cmeta:id="h2.phi2_c2" name="phi2_c2" public_interface="in" units="per_second" />
    <variable cmeta:id="h2.phi3_c2" name="phi3_c2" public_interface="in" units="per_second" />
    <variable cmeta:id="h2.h2" initial_value="0.1" name="h2" public_interface="out" units="dimensionless" />
    <variable cmeta:id="h2.phi_1_c2" name="phi_1_c2" public_interface="in" units="per_second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>h2</ci>
        </apply>
        <apply>
          <minus />
          <apply>
            <times />
            <ci>phi3_c2</ci>
            <apply>
              <minus />
              <cn xmlns:cellml="http://www.cellml.org/cellml/1.1#" cellml:units="dimensionless">1</cn>
              <ci>h2</ci>
            </apply>
          </apply>
          <apply>
            <divide />
            <apply>
              <times />
              <ci>phi1_c2</ci>
              <ci>phi2_c2</ci>
              <ci>h2</ci>
              <ci>p</ci>
            </apply>
            <apply>
              <plus />
              <apply>
                <times />
                <ci>phi1_c2</ci>
                <ci>p</ci>
              </apply>
              <ci>phi_1_c2</ci>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  <component name="j_pump">
    <variable cmeta:id="j_pump.j_pump_c2" name="j_pump_c2" public_interface="out" units="micro_molar_per_second" />
    <variable cmeta:id="j_pump.Vp" name="Vp" public_interface="in" units="micro_molar_per_second" />
    <variable cmeta:id="j_pump_j_pump_c1" name="j_pump_c1" public_interface="out" units="micro_molar_per_second" />
    <variable cmeta:id="j_pump.c2" name="c2" public_interface="in" units="micro_molar" />
    <variable cmeta:id="j_pump.c1" name="c1" public_interface="in" units="micro_molar" />
    <variable cmeta:id="j_pump.Kp" name="Kp" public_interface="in" units="micro_molar" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <ci>j_pump_c1</ci>
        <apply>
          <divide />
          <apply>
            <times />
            <ci>Vp</ci>
            <apply>
              <power />
              <ci>c1</ci>
              <cn xmlns:cellml="http://www.cellml.org/cellml/1.1#" cellml:units="dimensionless">2</cn>
            </apply>
          </apply>
          <apply>
            <plus />
            <apply>
              <power />
              <ci>Kp</ci>
              <cn xmlns:cellml="http://www.cellml.org/cellml/1.1#" cellml:units="dimensionless">2</cn>
            </apply>
            <apply>
              <power />
              <ci>c1</ci>
              <cn xmlns:cellml="http://www.cellml.org/cellml/1.1#" cellml:units="dimensionless">2</cn>
            </apply>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>j_pump_c2</ci>
        <apply>
          <divide />
          <apply>
            <times />
            <ci>Vp</ci>
            <apply>
              <power />
              <ci>c2</ci>
              <cn xmlns:cellml="http://www.cellml.org/cellml/1.1#" cellml:units="dimensionless">2</cn>
            </apply>
          </apply>
          <apply>
            <plus />
            <apply>
              <power />
              <ci>Kp</ci>
              <cn xmlns:cellml="http://www.cellml.org/cellml/1.1#" cellml:units="dimensionless">2</cn>
            </apply>
            <apply>
              <power />
              <ci>c2</ci>
              <cn xmlns:cellml="http://www.cellml.org/cellml/1.1#" cellml:units="dimensionless">2</cn>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  <component name="j_receptor">
    <variable cmeta:id="j_receptor.phi_1_c2" name="phi_1_c2" public_interface="in" units="per_second" />
    <variable cmeta:id="j_receptor.phi_1_c1" name="phi_1_c1" public_interface="in" units="per_second" />
    <variable cmeta:id="j_receptor.h1" name="h1" public_interface="in" units="dimensionless" />
    <variable cmeta:id="j_receptor.phi1_c2" name="phi1_c2" public_interface="in" units="second_order_rate" />
    <variable cmeta:id="j_receptor.h2" name="h2" public_interface="in" units="dimensionless" />
    <variable cmeta:id="j_receptor.phi1_c1" name="phi1_c1" public_interface="in" units="second_order_rate" />
    <variable cmeta:id="j_receptor.kf" name="kf" public_interface="in" units="micro_molar_per_second" />
    <variable cmeta:id="j_receptor.j_receptor_c2" name="j_receptor_c2" public_interface="out" units="micro_molar_per_second" />
    <variable cmeta:id="j_receptor.p" name="p" public_interface="in" units="micro_molar" />
    <variable cmeta:id="j_receptor_j_receptor_c1" name="j_receptor_c1" public_interface="out" units="micro_molar_per_second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <ci>j_receptor_c1</ci>
        <apply>
          <times />
          <ci>kf</ci>
          <apply>
            <power />
            <apply>
              <divide />
              <apply>
                <times />
                <ci>p</ci>
                <ci>h1</ci>
                <ci>phi1_c1</ci>
              </apply>
              <apply>
                <plus />
                <apply>
                  <times />
                  <ci>phi1_c1</ci>
                  <ci>p</ci>
                </apply>
                <ci>phi_1_c1</ci>
              </apply>
            </apply>
            <cn xmlns:cellml="http://www.cellml.org/cellml/1.1#" cellml:units="dimensionless">4</cn>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>j_receptor_c2</ci>
        <apply>
          <times />
          <ci>kf</ci>
          <apply>
            <power />
            <apply>
              <divide />
              <apply>
                <times />
                <ci>p</ci>
                <ci>h2</ci>
                <ci>phi1_c2</ci>
              </apply>
              <apply>
                <plus />
                <apply>
                  <times />
                  <ci>phi1_c2</ci>
                  <ci>p</ci>
                </apply>
                <ci>phi_1_c2</ci>
              </apply>
            </apply>
            <cn xmlns:cellml="http://www.cellml.org/cellml/1.1#" cellml:units="dimensionless">4</cn>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  <component name="model_parameters">
    <variable cmeta:id="model_parameters.Vp" initial_value="1.2" name="Vp" public_interface="out" units="micro_molar_per_second" />
    <variable cmeta:id="model_parameters.kf" initial_value="28" name="kf" public_interface="out" units="micro_molar_per_second" />
    <variable cmeta:id="model_parameters.D" initial_value="0.01" name="D" public_interface="out" units="per_second" />
    <variable cmeta:id="model_parameters.r4" initial_value="20" name="r4" public_interface="out" units="per_second" />
    <variable cmeta:id="model_parameters.R5" initial_value="1.6" name="R5" public_interface="out" units="micro_molar" />
    <variable cmeta:id="model_parameters.r2" initial_value="100" name="r2" public_interface="out" units="second_order_rate" />
    <variable cmeta:id="model_parameters.R3" initial_value="50" name="R3" public_interface="out" units="micro_molar" />
    <variable cmeta:id="model_parameters.R1" initial_value="6" name="R1" public_interface="out" units="micro_molar" />
    <variable cmeta:id="model_parameters.k3" initial_value="1.6" name="k3" public_interface="out" units="micro_molar_per_second" />
    <variable cmeta:id="model_parameters.k1" initial_value="44" name="k1" public_interface="out" units="micro_molar_per_second" />
    <variable cmeta:id="model_parameters.k2" initial_value="26.5" name="k2" public_interface="out" units="micro_molar_per_second" />
    <variable cmeta:id="model_parameters.Kp" initial_value="0.18" name="Kp" public_interface="out" units="micro_molar" />
    <variable cmeta:id="model_parameters.p" initial_value="0.2778" name="p" public_interface="out" units="micro_molar" />
    <variable cmeta:id="model_parameters_j_leak" initial_value="0.2" name="j_leak" public_interface="out" units="micro_molar_per_second" />
  </component>
  <component name="h1">
    <variable cmeta:id="h1.phi1_c1" name="phi1_c1" public_interface="in" units="second_order_rate" />
    <variable cmeta:id="h1.p" name="p" public_interface="in" units="micro_molar" />
    <variable cmeta:id="h1.phi2_c1" name="phi2_c1" public_interface="in" units="per_second" />
    <variable cmeta:id="h1.phi3_c1" name="phi3_c1" public_interface="in" units="per_second" />
    <variable cmeta:id="h1.phi_1_c1" name="phi_1_c1" public_interface="in" units="per_second" />
    <variable cmeta:id="h1.h1" initial_value="0.8" name="h1" public_interface="out" units="dimensionless" />
    <variable cmeta:id="h1.time" name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>h1</ci>
        </apply>
        <apply>
          <minus />
          <apply>
            <times />
            <ci>phi3_c1</ci>
            <apply>
              <minus />
              <cn xmlns:cellml="http://www.cellml.org/cellml/1.1#" cellml:units="dimensionless">1</cn>
              <ci>h1</ci>
            </apply>
          </apply>
          <apply>
            <divide />
            <apply>
              <times />
              <ci>phi1_c1</ci>
              <ci>phi2_c1</ci>
              <ci>h1</ci>
              <ci>p</ci>
            </apply>
            <apply>
              <plus />
              <apply>
                <times />
                <ci>phi1_c1</ci>
                <ci>p</ci>
              </apply>
              <ci>phi_1_c1</ci>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  <component name="j_diffusion">
    <variable cmeta:id="j_diffusion.D" name="D" public_interface="in" units="per_second" />
    <variable cmeta:id="j_diffusion.j_diffusion" name="j_diffusion" public_interface="out" units="micro_molar_per_second" />
    <variable cmeta:id="j_diffusion.c1" name="c1" public_interface="in" units="micro_molar" />
    <variable cmeta:id="j_diffusion.c2" name="c2" public_interface="in" units="micro_molar" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <ci>j_diffusion</ci>
        <apply>
          <times />
          <ci>D</ci>
          <apply>
            <minus />
            <ci>c2</ci>
            <ci>c1</ci>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  <component name="phi">
    <variable cmeta:id="phi.k1" name="k1" public_interface="in" units="micro_molar_per_second" />
    <variable cmeta:id="phi.k3" name="k3" public_interface="in" units="micro_molar_per_second" />
    <variable cmeta:id="phi.k2" name="k2" public_interface="in" units="micro_molar_per_second" />
    <variable cmeta:id="phi.r4" name="r4" public_interface="in" units="per_second" />
    <variable cmeta:id="phi.R3" name="R3" public_interface="in" units="micro_molar" />
    <variable cmeta:id="phi.R5" name="R5" public_interface="in" units="micro_molar" />
    <variable cmeta:id="phi.c1" name="c1" public_interface="in" units="micro_molar" />
    <variable cmeta:id="phi.phi_1_c2" name="phi_1_c2" public_interface="out" units="per_second" />
    <variable cmeta:id="phi.c2" name="c2" public_interface="in" units="micro_molar" />
    <variable cmeta:id="phi.phi_1_c1" name="phi_1_c1" public_interface="out" units="per_second" />
    <variable cmeta:id="phi.phi1_c1" name="phi1_c1" public_interface="out" units="second_order_rate" />
    <variable cmeta:id="phi.phi2_c2" name="phi2_c2" public_interface="out" units="per_second" />
    <variable cmeta:id="phi.phi1_c2" name="phi1_c2" public_interface="out" units="second_order_rate" />
    <variable cmeta:id="phi.phi3_c2" name="phi3_c2" public_interface="out" units="per_second" />
    <variable cmeta:id="phi.phi2_c1" name="phi2_c1" public_interface="out" units="per_second" />
    <variable cmeta:id="phi.phi3_c1" name="phi3_c1" public_interface="out" units="per_second" />
    <variable cmeta:id="phi.r2" name="r2" public_interface="in" units="second_order_rate" />
    <variable cmeta:id="phi.R1" name="R1" public_interface="in" units="micro_molar" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <ci>phi1_c1</ci>
        <apply>
          <divide />
          <apply>
            <times />
            <ci>r2</ci>
            <ci>c1</ci>
          </apply>
          <apply>
            <plus />
            <ci>R1</ci>
            <ci>c1</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>phi_1_c1</ci>
        <apply>
          <divide />
          <ci>k1</ci>
          <apply>
            <plus />
            <ci>R3</ci>
            <ci>c1</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>phi2_c1</ci>
        <apply>
          <divide />
          <apply>
            <plus />
            <ci>k2</ci>
            <apply>
              <times />
              <ci>r4</ci>
              <ci>c1</ci>
            </apply>
          </apply>
          <apply>
            <plus />
            <ci>R3</ci>
            <ci>c1</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>phi3_c1</ci>
        <apply>
          <divide />
          <ci>k3</ci>
          <apply>
            <plus />
            <ci>R5</ci>
            <ci>c1</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>phi1_c2</ci>
        <apply>
          <divide />
          <apply>
            <times />
            <ci>r2</ci>
            <ci>c2</ci>
          </apply>
          <apply>
            <plus />
            <ci>R1</ci>
            <ci>c2</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>phi_1_c2</ci>
        <apply>
          <divide />
          <ci>k1</ci>
          <apply>
            <plus />
            <ci>R3</ci>
            <ci>c2</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>phi2_c2</ci>
        <apply>
          <divide />
          <apply>
            <plus />
            <ci>k2</ci>
            <apply>
              <times />
              <ci>r4</ci>
              <ci>c2</ci>
            </apply>
          </apply>
          <apply>
            <plus />
            <ci>R3</ci>
            <ci>c2</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>phi3_c2</ci>
        <apply>
          <divide />
          <ci>k3</ci>
          <apply>
            <plus />
            <ci>R5</ci>
            <ci>c2</ci>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  <component name="c2">
    <variable cmeta:id="c2.c2" initial_value="0.1" name="c2" public_interface="out" units="micro_molar" />
    <variable cmeta:id="c2.j_pump_c2" name="j_pump_c2" public_interface="in" units="micro_molar_per_second" />
    <variable cmeta:id="c2.time" name="time" public_interface="in" units="second" />
    <variable cmeta:id="c2.j_diffusion" name="j_diffusion" public_interface="in" units="micro_molar_per_second" />
    <variable cmeta:id="c2.j_leak" name="j_leak" public_interface="in" units="micro_molar_per_second" />
    <variable cmeta:id="c2.j_receptor_c2" name="j_receptor_c2" public_interface="in" units="micro_molar_per_second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>c2</ci>
        </apply>
        <apply>
          <plus />
          <apply>
            <minus />
            <ci>j_receptor_c2</ci>
            <ci>j_pump_c2</ci>
          </apply>
          <ci>j_leak</ci>
          <ci>j_diffusion</ci>
        </apply>
      </apply>
    </math>
  </component>
  <component name="c1">
    <variable cmeta:id="c1.c1" initial_value="0.3" name="c1" public_interface="out" units="micro_molar" />
    <variable cmeta:id="c1.j_diffusion" name="j_diffusion" public_interface="in" units="micro_molar_per_second" />
    <variable cmeta:id="c1.time" name="time" public_interface="in" units="second" />
    <variable cmeta:id="c1.j_pump_c1" name="j_pump_c1" public_interface="in" units="micro_molar_per_second" />
    <variable cmeta:id="c1.j_leak" name="j_leak" public_interface="in" units="micro_molar_per_second" />
    <variable cmeta:id="c1.j_receptor_c1" name="j_receptor_c1" public_interface="in" units="micro_molar_per_second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>c1</ci>
        </apply>
        <apply>
          <plus />
          <apply>
            <minus />
            <ci>j_receptor_c1</ci>
            <ci>j_pump_c1</ci>
          </apply>
          <ci>j_leak</ci>
          <ci>j_diffusion</ci>
        </apply>
      </apply>
    </math>
  </component>
  <component name="environment">
    <variable cmeta:id="environment_time" name="time" public_interface="out" units="second" />
  </component>
  <connection>
    <map_components component_1="model_parameters" component_2="c1" />
    <map_variables variable_1="j_leak" variable_2="j_leak" />
  </connection>
  <connection>
    <map_components component_1="model_parameters" component_2="j_pump" />
    <map_variables variable_1="Vp" variable_2="Vp" />
    <map_variables variable_1="Kp" variable_2="Kp" />
  </connection>
  <connection>
    <map_components component_1="c2" component_2="j_pump" />
    <map_variables variable_1="c2" variable_2="c2" />
  </connection>
  <connection>
    <map_components component_1="h1" component_2="j_receptor" />
    <map_variables variable_1="h1" variable_2="h1" />
  </connection>
  <connection>
    <map_components component_1="environment" component_2="h1" />
    <map_variables variable_1="time" variable_2="time" />
  </connection>
  <connection>
    <map_components component_1="j_pump" component_2="c2" />
    <map_variables variable_1="j_pump_c2" variable_2="j_pump_c2" />
  </connection>
  <connection>
    <map_components component_1="phi" component_2="j_receptor" />
    <map_variables variable_1="phi1_c1" variable_2="phi1_c1" />
    <map_variables variable_1="phi_1_c2" variable_2="phi_1_c2" />
    <map_variables variable_1="phi_1_c1" variable_2="phi_1_c1" />
    <map_variables variable_1="phi1_c2" variable_2="phi1_c2" />
  </connection>
  <connection>
    <map_components component_1="environment" component_2="c1" />
    <map_variables variable_1="time" variable_2="time" />
  </connection>
  <connection>
    <map_components component_1="environment" component_2="c2" />
    <map_variables variable_1="time" variable_2="time" />
  </connection>
  <connection>
    <map_components component_1="phi" component_2="h1" />
    <map_variables variable_1="phi1_c1" variable_2="phi1_c1" />
    <map_variables variable_1="phi2_c1" variable_2="phi2_c1" />
    <map_variables variable_1="phi_1_c1" variable_2="phi_1_c1" />
    <map_variables variable_1="phi3_c1" variable_2="phi3_c1" />
  </connection>
  <connection>
    <map_components component_1="j_receptor" component_2="c2" />
    <map_variables variable_1="j_receptor_c2" variable_2="j_receptor_c2" />
  </connection>
  <connection>
    <map_components component_1="model_parameters" component_2="j_diffusion" />
    <map_variables variable_1="D" variable_2="D" />
  </connection>
  <connection>
    <map_components component_1="model_parameters" component_2="phi" />
    <map_variables variable_1="R3" variable_2="R3" />
    <map_variables variable_1="r4" variable_2="r4" />
    <map_variables variable_1="k2" variable_2="k2" />
    <map_variables variable_1="R5" variable_2="R5" />
    <map_variables variable_1="k1" variable_2="k1" />
    <map_variables variable_1="r2" variable_2="r2" />
    <map_variables variable_1="k3" variable_2="k3" />
    <map_variables variable_1="R1" variable_2="R1" />
  </connection>
  <connection>
    <map_components component_1="j_pump" component_2="c1" />
    <map_variables variable_1="j_pump_c1" variable_2="j_pump_c1" />
  </connection>
  <connection>
    <map_components component_1="j_diffusion" component_2="c1" />
    <map_variables variable_1="j_diffusion" variable_2="j_diffusion" />
  </connection>
  <connection>
    <map_components component_1="c2" component_2="j_diffusion" />
    <map_variables variable_1="c2" variable_2="c2" />
  </connection>
  <connection>
    <map_components component_1="h2" component_2="j_receptor" />
    <map_variables variable_1="h2" variable_2="h2" />
  </connection>
  <connection>
    <map_components component_1="j_receptor" component_2="c1" />
    <map_variables variable_1="j_receptor_c1" variable_2="j_receptor_c1" />
  </connection>
  <connection>
    <map_components component_1="model_parameters" component_2="h2" />
    <map_variables variable_1="p" variable_2="p" />
  </connection>
  <connection>
    <map_components component_1="model_parameters" component_2="j_receptor" />
    <map_variables variable_1="kf" variable_2="kf" />
    <map_variables variable_1="p" variable_2="p" />
  </connection>
  <connection>
    <map_components component_1="c1" component_2="j_pump" />
    <map_variables variable_1="c1" variable_2="c1" />
  </connection>
  <connection>
    <map_components component_1="model_parameters" component_2="h1" />
    <map_variables variable_1="p" variable_2="p" />
  </connection>
  <connection>
    <map_components component_1="environment" component_2="h2" />
    <map_variables variable_1="time" variable_2="time" />
  </connection>
  <connection>
    <map_components component_1="j_diffusion" component_2="c2" />
    <map_variables variable_1="j_diffusion" variable_2="j_diffusion" />
  </connection>
  <connection>
    <map_components component_1="c2" component_2="phi" />
    <map_variables variable_1="c2" variable_2="c2" />
  </connection>
  <connection>
    <map_components component_1="phi" component_2="h2" />
    <map_variables variable_1="phi2_c2" variable_2="phi2_c2" />
    <map_variables variable_1="phi_1_c2" variable_2="phi_1_c2" />
    <map_variables variable_1="phi1_c2" variable_2="phi1_c2" />
    <map_variables variable_1="phi3_c2" variable_2="phi3_c2" />
  </connection>
  <connection>
    <map_components component_1="c1" component_2="j_diffusion" />
    <map_variables variable_1="c1" variable_2="c1" />
  </connection>
  <connection>
    <map_components component_1="model_parameters" component_2="c2" />
    <map_variables variable_1="j_leak" variable_2="j_leak" />
  </connection>
  <connection>
    <map_components component_1="c1" component_2="phi" />
    <map_variables variable_1="c1" variable_2="c1" />
  </connection>
</model>