Location: Noble 1962 model for Physiome article @ aeb0c953cfd0 / 1962_noble.xml

Author:
David Nickerson <nickerso@users.sourceforge.net>
Date:
2017-07-06 16:36:33+12:00
Desc:
adding initial versions of the CellML models as published at: http://www.physiome.org.nz/publications/PBMB-2006-90/Nickerson/
Permanent Source URI:
https://models.physiomeproject.org/workspace/49e/rawfile/aeb0c953cfd08e3f4649ce2b572fe7bc8ad4e760/1962_noble.xml

<?xml version="1.0" encoding="iso-8859-1"?>

<model
    name="noble_model_1962"
    cmeta:id="noble_model_1962"
    xmlns="http://www.cellml.org/cellml/1.0#"
    xmlns:cellml="http://www.cellml.org/cellml/1.0#"
    xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
  <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#"
      xmlns:bqs="http://www.cellml.org/bqs/1.0#"
      xmlns:dc="http://purl.org/dc/elements/1.1/"
      xmlns:dcterms="http://purl.org/dc/terms/"
      xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">
    <!--
      The following RDF block contains metadata that applies to this document
      as a whole, as indicated by the empty about attribute on the 
      <rdf:Description> element.
    -->
    <rdf:Description rdf:about="">
      <!--
        The Model Builder Metadata.  The Dublin Core "creator" element is used  
        to indicate the person who translated the model into CellML.
      -->
      <dc:creator rdf:parseType="Resource">
        <vCard:N rdf:parseType="Resource">
          <vCard:Family>Lloyd</vCard:Family>
          <vCard:Given>Catherine</vCard:Given>
          <vCard:Other>May</vCard:Other>
        </vCard:N>
        <vCard:EMAIL rdf:parseType="Resource">
          <rdf:value>c.lloyd@auckland.ac.nz</rdf:value>
          <rdf:type rdf:resource="http://imc.org/vCard/3.0#internet" />
        </vCard:EMAIL>
        <vCard:ORG rdf:parseType="Resource">
          <vCard:Orgname>The University of Auckland</vCard:Orgname>
          <vCard:Orgunit>Bioengineering Institute</vCard:Orgunit>
        </vCard:ORG>
      </dc:creator>
      
      <!--
        The Creation Date metadata. This is the date on which the model
        was translated into CellML.
      -->
      <dcterms:created rdf:parseType="Resource">
        <dcterms:W3CDTF>2001-12-18</dcterms:W3CDTF>
      </dcterms:created>
      
      <!--
        The Modification History metadata. This lists the changes that have been
        made to the document, who made the changes, and when they were made.
      -->
      <cmeta:modification rdf:parseType="Resource">
        <rdf:value>
          Encapsulated the model under an interface component for use when
          importing the model into a specific experiment or simulation.
        </rdf:value>
        <cmeta:modifier rdf:parseType="Resource">
          <vCard:N rdf:parseType="Resource">
            <vCard:Family>Nickerson</vCard:Family>
            <vCard:Given>David</vCard:Given>
            <vCard:Other>P</vCard:Other>
          </vCard:N>
        </cmeta:modifier>
        <dcterms:modified rdf:parseType="Resource"> 
          <dcterms:W3CDTF>2004-12-21</dcterms:W3CDTF>
        </dcterms:modified>
      </cmeta:modification>
      <cmeta:modification rdf:parseType="Resource">
        <rdf:value>
          Changed units and added stimulus current.
        </rdf:value>
        <cmeta:modifier rdf:parseType="Resource">
          <vCard:N rdf:parseType="Resource">
            <vCard:Family>Nickerson</vCard:Family>
            <vCard:Given>David</vCard:Given>
            <vCard:Other>P</vCard:Other>
          </vCard:N>
        </cmeta:modifier>
        <dcterms:modified rdf:parseType="Resource"> 
          <dcterms:W3CDTF>2003-04-05</dcterms:W3CDTF>
        </dcterms:modified>
      </cmeta:modification>
      <cmeta:modification rdf:parseType="Resource">
        <rdf:value>
          Changed the model name so the model loads in the database easier.
        </rdf:value>
        <cmeta:modifier rdf:parseType="Resource">
          <vCard:N rdf:parseType="Resource">
            <vCard:Family>Cuellar</vCard:Family>
            <vCard:Given>Autumn</vCard:Given>
            <vCard:Other>A</vCard:Other>
          </vCard:N>
        </cmeta:modifier>
        <dcterms:modified rdf:parseType="Resource"> 
          <dcterms:W3CDTF>2003-04-05</dcterms:W3CDTF>
        </dcterms:modified>
      </cmeta:modification>
      <cmeta:modification rdf:parseType="Resource">
        <rdf:value>
          Corrected membrane_voltage_diff_eq.
        </rdf:value>
        <cmeta:modifier rdf:parseType="Resource">
          <vCard:N rdf:parseType="Resource">
            <vCard:Family>Lloyd</vCard:Family>
            <vCard:Given>Catherine</vCard:Given>
            <vCard:Other>May</vCard:Other>
          </vCard:N>
        </cmeta:modifier>
        <dcterms:modified rdf:parseType="Resource"> 
          <dcterms:W3CDTF>2002-02-28</dcterms:W3CDTF>
        </dcterms:modified>
      </cmeta:modification>
      <cmeta:modification rdf:parseType="Resource">
        <rdf:value>
          Updated metadata to conform to the 16/01/2002 CellML Metadata 1.0 
          Specification.
        </rdf:value>
        <cmeta:modifier rdf:parseType="Resource">
          <vCard:N rdf:parseType="Resource">
            <vCard:Family>Cuellar</vCard:Family>
            <vCard:Given>Autumn</vCard:Given>
            <vCard:Other>A.</vCard:Other>
          </vCard:N>
        </cmeta:modifier>
        <dcterms:modified rdf:parseType="Resource"> 
          <dcterms:W3CDTF>2002-01-20</dcterms:W3CDTF>
        </dcterms:modified>
      </cmeta:modification>
      <!-- The Publisher metadata. -->
      <dc:publisher>
        Bioengineering Institute, The University of Auckland.
      </dc:publisher>
    </rdf:Description>
    
    <!--
      The following metadata refers to the model itself, as indicated by the
      reference to the ID "noble_model_1962", which is declared on the    
      <model> element.
    -->
    <rdf:Description rdf:about="#noble_model_1962">
      <!-- A human readable name for the model. -->
      <dc:title>
        The 1962 Noble Model of Purkinje Fibre Action and Pace-maker Potentials
      </dc:title>

      <!-- A comment regarding the model. -->
      <cmeta:comment rdf:parseType="Resource">
        <rdf:value>
          This is the CellML description of Noble's 1962 mathematical model of
          Purkinje fibre action and pace-maker potentials.  The equations 
          formulated by Hodgkin and Huxley (1952) to describe the electrical 
          activity of squid nerve have been modified to describe the action
          and pace-maker potentials of the Purkinje fibres of the heart.
        </rdf:value>
        <!-- The creator of the comment. -->
        <dc:creator rdf:parseType="Resource">
          <vCard:FN>Catherine Lloyd</vCard:FN>
        </dc:creator>
      </cmeta:comment>

      <!-- The model is relevant to all mammals. -->
      <cmeta:species>Mammalia</cmeta:species>

      <bqs:reference rdf:parseType="Resource">
        <bqs:Pubmed_id>14480151</bqs:Pubmed_id>
        <bqs:JournalArticle rdf:parseType="Resource">
          <dc:creator rdf:parseType="Resource">
            <bqs:Person rdf:parseType="Resource">
              <vCard:N rdf:parseType="Resource">
                <vCard:Family>Noble</vCard:Family>
                <vCard:Given>Denis</vCard:Given>
              </vCard:N>
            </bqs:Person>
          </dc:creator>
          <dc:title>
            A Modification of the Hodgkin-Huxley Equations Applicable to
            Purkinje Fibre Action and Pace-maker Potentials
          </dc:title>
          <dcterms:issued rdf:parseType="Resource">
            <dcterms:W3CDTF>1962</dcterms:W3CDTF>
          </dcterms:issued>
          <bqs:Journal rdf:parseType="Resource">
            <dc:title>Journal of Physiology</dc:title>
          </bqs:Journal>
          <bqs:volume>160</bqs:volume>
          <bqs:first_page>317</bqs:first_page>
          <bqs:last_page>352</bqs:last_page>
        </bqs:JournalArticle>
      </bqs:reference>
    </rdf:Description>
  </rdf:RDF>

  <!--
    Below, we define some additional units for association with variables and
    constants within the model. The identifiers are fairly self-explanatory.
  -->
  <units name="ms">
    <unit prefix="milli" units="second" />
  </units>
  
  <units name="per_ms">
    <unit prefix="milli" units="second" exponent="-1" />
  </units>

  <units name="mV">
    <unit prefix="milli" units="volt" />
  </units>

  <units name="per_mV">
    <unit prefix="milli" units="volt" exponent="-1" />
  </units>
  
  <units name="per_mV_ms">
    <unit units="mV" exponent="-1" />
    <unit units="ms" exponent="-1" />
  </units>
  
  <units name="mS_per_mm2">
    <unit prefix="milli" units="siemens" />
    <unit prefix="milli" units="metre" exponent="-2" />
  </units>

  <units name="uF_per_mm2">
    <unit prefix="micro" units="farad" />
    <unit prefix="milli" units="metre" exponent="-2" />
  </units>

  <units name="uA_per_mm2">
    <unit prefix="micro" units="ampere" />
    <unit prefix="milli" units="metre" exponent="-2" />
  </units>
   
  <component name="interface" cmeta:id="interface">
    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#interface">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            Here we define a component which encapsulates the entire model
            and provides the interface to model boundary conditions and
            outputs.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>
    <!-- time is always a special case -->
    <variable name="time" public_interface="in" private_interface="out" units="ms"/>
    <!-- inputs -->
    <variable name="I_stim" public_interface="in" private_interface="out" units="uA_per_mm2"/>
    <variable name="g_K_add" public_interface="in" private_interface="out" units="mS_per_mm2" />
    <!-- outputs -->
  </component><!--interface-->
   
  <!--
    The "membrane" component is really the `root' node of our model.
    It defines the action potential variable "V" among other things.
  -->
  <component name="membrane" cmeta:id="membrane">
    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#membrane">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            The main component of the model, containing the membrane currents
            and defining the transmembrane potential.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>

    <variable name="V" initial_value="-73.8" public_interface="out" units="mV" />
    <variable name="Cm" initial_value="0.12" units="uF_per_mm2" />
    <variable name="time" public_interface="in" units="ms" />
    <variable name="i_Na" public_interface="in" units="uA_per_mm2" />
    <variable name="i_K" public_interface="in" units="uA_per_mm2" />
    <variable name="i_Leak" public_interface="in" units="uA_per_mm2" />
    <variable name="I_stim" public_interface="in" units="uA_per_mm2" />

    <!--
      The membrane voltage (V) is calculated as an ordinary
      differential equation in terms of the currents.
    -->
    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#membrane_voltage_diff_eq">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            The kinetics of the transmembrane potential.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>
    <math xmlns="http://www.w3.org/1998/Math/MathML"
      cmeta:id="membrane_voltage_diff_eq">
      <apply id="membrane_voltage_diff_eq"><eq />
        <apply><diff />
          <bvar><ci> time </ci></bvar>
          <ci> V </ci>
        </apply>
        <apply><divide />
          <apply><minus />
            <ci>I_stim</ci>
            <apply><plus />
              <ci> i_Na </ci>
              <ci> i_K </ci>
              <ci> i_Leak </ci>
            </apply>
          </apply>
          <ci> Cm </ci>
        </apply>
      </apply>
    </math>
    
    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#IStim_for_cmiss_eq">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            This is a dummy equation that we simply use to make grabbing the
            value easier.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>
    <variable name="IStimC" units="uA_per_mm2" public_interface="out"/>
    <math xmlns="http://www.w3.org/1998/Math/MathML" cmeta:id="IStim_for_cmiss_eq">
      <apply id="IStim_for_cmiss"><eq/>
        <ci>IStimC</ci>
        <ci>I_stim</ci>
      </apply>
    </math>
  </component>
  
  <component name="sodium_channel" cmeta:id="sodium_channel">
    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#sodium_channel">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            The modified sodium current from the 1952 Hodgkin Huxley model.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>

    <variable name="i_Na" public_interface="out" units="uA_per_mm2" />
    <variable name="g_Na_max" initial_value="4.0" units="mS_per_mm2" />
    <variable name="g_Na" units="mS_per_mm2" />
    <variable name="E_Na" initial_value="40.0" units="mV" />
    <variable
        name="time" public_interface="in"
        private_interface="out" units="ms" />
    <variable
        name="V" public_interface="in"
        private_interface="out" units="mV" />
    <variable name="m" private_interface="in" units="dimensionless" />
    <variable name="h" private_interface="in" units="dimensionless" />

    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#g_Na_calculation_eq">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            Calculation of the channel conductance.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>
    <math xmlns="http://www.w3.org/1998/Math/MathML"
      cmeta:id="g_Na_calculation_eq">
      <apply id="g_Na_calculation"><eq />
        <ci> g_Na </ci>
        <apply><times />
          <apply><power />
            <ci> m </ci>
            <cn cellml:units="dimensionless"> 3.0 </cn>
          </apply>
          <ci> h </ci>
          <ci> g_Na_max </ci>
        </apply>
      </apply>
    </math>
      
    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#i_Na_calculation_eq">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            Calculation of the channel current.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>
    <math xmlns="http://www.w3.org/1998/Math/MathML"
      cmeta:id="i_Na_calculation_eq">
      <apply id="i_Na_calculation"><eq />
        <ci> i_Na </ci>
        <apply><times />
          <apply><plus />
            <apply><times />
              <ci> g_Na_max </ci>
              <apply><power />
                <ci> m </ci>
                <cn cellml:units="dimensionless"> 3.0 </cn>
              </apply>
              <ci> h </ci>
            </apply>
            <cn cellml:units="mS_per_mm2">0.14e-2</cn>
          </apply>
          <apply><minus />
            <ci> V </ci>
            <ci> E_Na </ci>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
      
  <component name="sodium_channel_m_gate" cmeta:id="sodium_channel_m_gate">
    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#sodium_channel_m_gate">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            The voltage-dependent activation gate for the sodium channel - the m
            gate.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>

    <variable name="m" initial_value="0.05" public_interface="out" units="dimensionless" />
    <variable name="alpha_m" units="per_ms" />
    <variable name="beta_m" units="per_ms" />
    <variable name="V" public_interface="in" units="mV" />
    <variable name="time" public_interface="in" units="ms" />

    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#alpha_m_calculation_eq">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            The opening rate for the m gate.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>
    <math xmlns="http://www.w3.org/1998/Math/MathML"
      cmeta:id="alpha_m_calculation_eq">
      <apply id="alpha_m_calculation"><eq />
        <ci> alpha_m </ci>
        <apply><divide />
          <apply><times />
            <cn cellml:units="per_mV_ms"> 0.1 </cn>
            <apply><minus />
              <apply><minus />
                <ci> V </ci>
              </apply>
              <cn cellml:units="mV"> 48.0 </cn>
            </apply>
          </apply>
          <apply><minus />
            <apply><exp />
              <apply><divide />
                <apply><minus />
                  <apply><minus />
                    <ci> V </ci>
                  </apply>
                  <cn cellml:units="mV"> 48.0 </cn>
                </apply>
                <cn cellml:units="mV"> 15.0 </cn>
              </apply>
            </apply>
            <cn cellml:units="dimensionless"> 1.0 </cn>
          </apply>
        </apply>
      </apply>
    </math>
      
    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#beta_m_calculation_eq">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            The closing rate for the m gate.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>
    <math xmlns="http://www.w3.org/1998/Math/MathML"
      cmeta:id="beta_m_calculation_eq">
      <apply id="beta_m_calculation"><eq />
        <ci> beta_m </ci>
        <apply><divide />
          <apply><times />
            <cn cellml:units="per_mV_ms"> 0.12 </cn>
            <apply><plus />
              <ci> V </ci>
              <cn cellml:units="mV"> 8.0 </cn>
            </apply>
          </apply>
          <apply><minus />
            <apply><exp />
              <apply><divide />
                <apply><plus />
                  <ci> V </ci>
                  <cn cellml:units="mV"> 8.0 </cn>
                </apply>
                <cn cellml:units="mV"> 5.0 </cn>
              </apply>
            </apply>
            <cn cellml:units="dimensionless"> 1.0 </cn>
          </apply>
        </apply>
      </apply>
    </math>
      
    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#dm_dt_eq">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            The kinetics of the m gate.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>
    <math xmlns="http://www.w3.org/1998/Math/MathML"
      cmeta:id="dm_dt_eq">
      <apply id="dm_dt"><eq />
        <apply><diff />
          <bvar><ci> time </ci></bvar>
          <ci> m </ci>
        </apply>
        <apply><minus />
          <apply><times />
            <ci> alpha_m </ci>
            <apply><minus />
              <cn cellml:units="dimensionless"> 1.0 </cn>
              <ci> m </ci>
            </apply>
          </apply>
          <apply><times />
            <ci> beta_m </ci>
            <ci> m </ci>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="sodium_channel_h_gate" cmeta:id="sodium_channel_h_gate">
    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#sodium_channel_h_gate">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            The voltage-dependent inactivation gate for the sodium channel - the
            h gate.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>

    <variable name="h" initial_value="0.785" public_interface="out" units="dimensionless" />
    <variable name="alpha_h" units="per_ms" />
    <variable name="beta_h" units="per_ms" />
    <variable name="V" public_interface="in" units="mV" />
    <variable name="time" public_interface="in" units="ms" />

    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#alpha_h_calculation_eq">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            The opening rate for the h gate.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>
    <math xmlns="http://www.w3.org/1998/Math/MathML"
      cmeta:id="alpha_h_calculation_eq">
      <apply id="alpha_h_calculation"><eq />
        <ci> alpha_h </ci>       
        <apply><times />
          <cn cellml:units="per_ms"> 0.17 </cn>
          <apply><exp />
            <apply><divide />
              <apply><minus />
                <apply><minus />
                  <ci> V </ci>
                </apply>
                <cn cellml:units="mV"> 90.0 </cn>
              </apply>
              <cn cellml:units="mV"> 20.0 </cn>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
      
    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#beta_h_calculation_eq">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            The closing rate for the h gate.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>
    <math xmlns="http://www.w3.org/1998/Math/MathML"
      cmeta:id="beta_h_calculation_eq">
      <apply id="beta_h_calculation"><eq />
        <ci> beta_h </ci>
        <apply><divide />
          <cn cellml:units="per_ms"> 1.0 </cn>
          <apply><plus />
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <apply><exp />
              <apply><divide />
                <apply><minus />
                  <apply><minus />
                    <ci> V </ci>
                  </apply>
                  <cn cellml:units="mV"> 42.0 </cn>
                </apply>
                <cn cellml:units="mV"> 10.0 </cn>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
      
    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#dh_dt_eq">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            The kinetics of the h gate.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>
    <math xmlns="http://www.w3.org/1998/Math/MathML"
      cmeta:id="dh_dt_eq">
      <apply id="dh_dt"><eq />
        <apply><diff />
          <bvar><ci> time </ci></bvar>
          <ci> h </ci>
        </apply>
        <apply><minus />
          <apply><times />
            <ci> alpha_h </ci>
            <apply><minus />
              <cn cellml:units="dimensionless"> 1.0 </cn>
              <ci> h </ci>
            </apply>
          </apply>
          <apply><times />
            <ci> beta_h </ci>
            <ci> h </ci>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="potassium_channel" cmeta:id="potassium_channel">
    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#potassium_channel">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            The modified Hodgkin Huxley 1952 potassium channel.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>

    <variable name="i_K" public_interface="out" units="uA_per_mm2" />
    <variable name="g_K1" units="mS_per_mm2" />
    <variable name="g_K2" units="mS_per_mm2" />
    <variable name="g_K_add" public_interface="in" units="mS_per_mm2" />
    <variable
        name="time" public_interface="in"
        private_interface="out" units="ms" />
    <variable
        name="V" public_interface="in"
        private_interface="out" units="mV" />
    <variable name="n" private_interface="in" units="dimensionless" />

    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#i_K_calculation_eq">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            Calculation of the potassium current. The g_K_add conductance term
            can be used to obtain a quiescent variant of the model by setting
            its value to 0.001 mS/mm2.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>
    <math xmlns="http://www.w3.org/1998/Math/MathML"
      cmeta:id="i_K_calculation_eq">
      <apply id="i_K_calculation"><eq />
        <ci> i_K </ci>
        <apply><times />
          <apply><plus />
            <ci> g_K1 </ci>
            <ci> g_K2 </ci>
            <ci> g_K_add </ci>
          </apply>
          <apply><plus />
            <ci> V </ci>
            <cn cellml:units="mV"> 100.0 </cn>
          </apply>
        </apply>
      </apply>
    </math>
      
    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#g_K1_calculation_eq">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            The conductance of the first "type" of potassium channels present in
            this model, using an empirical formaulation.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>
    <math xmlns="http://www.w3.org/1998/Math/MathML"
      cmeta:id="g_K1_calculation_eq">
      <apply id="g_K1_calculation"><eq />
        <ci> g_K1 </ci>
        <apply><plus />
          <apply><times />
            <cn cellml:units="mS_per_mm2"> 1.2e-2 </cn>
            <apply><exp />
              <apply><divide />
                <apply><minus />
                  <apply><minus />
                    <ci> V </ci>
                  </apply>
                  <cn cellml:units="mV"> 90.0 </cn>
                </apply>
                <cn cellml:units="mV"> 50.0 </cn>
              </apply>
            </apply>
          </apply>
          <apply><times />
            <cn cellml:units="mS_per_mm2"> 0.015e-2 </cn>
            <apply><exp />
              <apply><divide />
                <apply><plus />
                  <ci> V </ci>
                  <cn cellml:units="mV"> 90.0 </cn>
                </apply>
                <cn cellml:units="mV"> 60.0 </cn>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
      
    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#g_K2_calculation_eq">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            The conductance of the second "type" of potassium channels present
            in this model, using the Hodgkin Huxley 1952 type kinetics.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>
    <math xmlns="http://www.w3.org/1998/Math/MathML"
      cmeta:id="g_K2_calculation_eq">
      <apply id="g_K2_calculation"><eq />
        <ci> g_K2 </ci>
        <apply><times />
          <cn cellml:units="mS_per_mm2"> 1.2e-2 </cn>
          <apply><power />
            <ci> n </ci>
            <cn cellml:units="dimensionless"> 4.0 </cn>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
    
  <component name="potassium_channel_n_gate" cmeta:id="potassium_channel_n_gate">
    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#potassium_channel_n_gate">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            The voltage-dependent activation gate for the potassium channel -
            the n gate.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>

    <variable name="n" initial_value="0.0935" public_interface="out" units="dimensionless" />
    <variable name="alpha_n" units="per_ms" />
    <variable name="beta_n" units="per_ms" />
    <variable name="V" public_interface="in" units="mV" />
    <variable name="time" public_interface="in" units="ms" />
    
    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#alpha_n_calculation_eq">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            The opening rate for the n gate.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>
    <math xmlns="http://www.w3.org/1998/Math/MathML"
      cmeta:id="alpha_n_calculation_eq">
      <apply id="alpha_n_calculation"><eq />
        <ci> alpha_n </ci>
        <apply><divide />
          <apply><times />
            <cn cellml:units="per_mV_ms"> 0.0001 </cn>
            <apply><minus />
              <apply><minus />
                <ci> V </ci>
              </apply>
              <cn cellml:units="mV"> 50.0 </cn>
            </apply>
          </apply>
          <apply><minus />
            <apply><exp />
              <apply><divide />
                <apply><minus />
                  <apply><minus />
                    <ci> V </ci>
                  </apply>
                  <cn cellml:units="mV"> 50.0 </cn>
                </apply>
                <cn cellml:units="mV"> 10.0 </cn>
              </apply>
            </apply>
            <cn cellml:units="dimensionless"> 1.0 </cn>
          </apply>
        </apply>
      </apply>
    </math>
      
    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#beta_n_calculation_eq">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            The closing rate for the n gate.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>
    <math xmlns="http://www.w3.org/1998/Math/MathML"
      cmeta:id="beta_n_calculation_eq">
      <apply id="beta_n_calculation"><eq />
        <ci> beta_n </ci>       
        <apply><times />
          <cn cellml:units="per_ms"> 0.002 </cn>
          <apply><exp />
            <apply><divide />
              <apply><minus />
                <apply><minus />
                  <ci> V </ci>
                </apply>
                <cn cellml:units="mV"> 90.0 </cn>
              </apply>
              <cn cellml:units="mV"> 80.0 </cn>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
      
    <rdf:RDF
      xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
      xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#dn_dt_eq">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            The kinetics of the n gate.
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>
    <math xmlns="http://www.w3.org/1998/Math/MathML"
      cmeta:id="dn_dt_eq">
      <apply id="dn_dt"><eq />
        <apply><diff />
          <bvar><ci> time </ci></bvar>
          <ci> n </ci>
        </apply>
        <apply><minus />
          <apply><times />
            <ci> alpha_n </ci>
            <apply><minus />
              <cn cellml:units="dimensionless"> 1.0 </cn>
              <ci> n </ci>
            </apply>
          </apply>
          <apply><times />
            <ci> beta_n </ci>
            <ci> n </ci>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="leakage_current" cmeta:id="leakage_current">
    <rdf:RDF
        xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
        xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
      <rdf:Description rdf:about="#leakage_current">
        <cmeta:comment rdf:parseType="Resource">
          <rdf:value>
            A non-specific background current attributed in part to chloride
            ions. Can be turned on by specifying an appropriate value for the
            conductance (~0.00075 mS/mm2).
          </rdf:value>
        </cmeta:comment>
      </rdf:Description>
    </rdf:RDF>
    <variable name="i_Leak" public_interface="out" units="uA_per_mm2" />
    <variable name="g_L" initial_value="0.0" units="mS_per_mm2" />
    <variable name="E_L" initial_value="-60.0" units="mV" />
    <variable name="time" public_interface="in" units="ms" />
    <variable name="V" public_interface="in" units="mV" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="i_Leak_calculation"><eq />
        <ci> i_Leak </ci>
        <apply><times />
          <ci> g_L </ci>
          <apply><minus />
            <ci> V </ci>
            <ci> E_L </ci>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <group>
    <relationship_ref relationship="containment" />
    <component_ref component="membrane">
      <component_ref component="sodium_channel">
        <component_ref component="sodium_channel_m_gate" />
        <component_ref component="sodium_channel_h_gate" />
      </component_ref>
      <component_ref component="potassium_channel">
        <component_ref component="potassium_channel_n_gate" />
      </component_ref>
      <component_ref component="leakage_current" />
    </component_ref>
  </group>
  
  <group>
    <relationship_ref relationship="encapsulation" />
    <component_ref component="interface">
      <component_ref component="membrane"/>
      <component_ref component="sodium_channel">
        <component_ref component="sodium_channel_m_gate" />
        <component_ref component="sodium_channel_h_gate" />
      </component_ref>
      <component_ref component="potassium_channel">
        <component_ref component="potassium_channel_n_gate" />
      </component_ref>
      <component_ref component="leakage_current" />
    </component_ref>
  </group>
  
  <connection>
    <map_components
        component_1="membrane" component_2="interface"/>
    <map_variables variable_1="time" variable_2="time"/>
    <map_variables variable_1="I_stim" variable_2="I_stim"/>
  </connection>


  <connection>
    <map_components
        component_1="sodium_channel" component_2="interface" />
    <map_variables variable_1="time" variable_2="time" />
  </connection>


  <connection>
    <map_components
        component_1="potassium_channel" component_2="interface"/>
    <map_variables variable_1="time" variable_2="time"/>
    <map_variables variable_1="g_K_add" variable_2="g_K_add"/>
  </connection>


  <connection>
    <map_components
        component_1="leakage_current" component_2="interface" />
    <map_variables variable_1="time" variable_2="time" />
  </connection>
  
  <connection>
    <map_components
        component_1="membrane" component_2="sodium_channel" />
    <map_variables variable_1="V" variable_2="V" />
    <map_variables variable_1="i_Na" variable_2="i_Na" />
  </connection>


  <connection>
    <map_components
        component_1="membrane" component_2="potassium_channel" />
    <map_variables variable_1="V" variable_2="V" />
    <map_variables variable_1="i_K" variable_2="i_K" />
  </connection>


  <connection>
    <map_components
        component_1="membrane" component_2="leakage_current" />
    <map_variables variable_1="V" variable_2="V" />
    <map_variables variable_1="i_Leak" variable_2="i_Leak" />
  </connection>
  
  <connection>
    <map_components
        component_1="sodium_channel" component_2="sodium_channel_m_gate" />
    <map_variables variable_1="m" variable_2="m" />
    <map_variables variable_1="time" variable_2="time" />
    <map_variables variable_1="V" variable_2="V" />
  </connection>


  <connection>
    <map_components
        component_1="sodium_channel" component_2="sodium_channel_h_gate" />
    <map_variables variable_1="h" variable_2="h" />
    <map_variables variable_1="time" variable_2="time" />
    <map_variables variable_1="V" variable_2="V" />
  </connection>


  <connection>
    <map_components
        component_1="potassium_channel"
        component_2="potassium_channel_n_gate" />
    <map_variables variable_1="n" variable_2="n" />
    <map_variables variable_1="time" variable_2="time" />
    <map_variables variable_1="V" variable_2="V" />
  </connection>


</model>