Location: Noble 1962 model for Physiome article @ c3db084a5fbb / 1962_noble.xml

Author:
David Nickerson <nickerso@users.sourceforge.net>
Date:
2017-07-06 16:36:34+12:00
Desc:
updating all imports to relative due to both the original website published versions now being unusable as XML documents and to be self contained in this PMR workspace
Permanent Source URI:
http://models.cellml.org/workspace/49e/rawfile/c3db084a5fbb011675fe7b2f74559d9b16fcc746/1962_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>