- Author:
- jlaw060 <jlaw060@bioeng203.bioeng.auckland.ac.nz>
- Date:
- 2009-06-26 16:09:13+12:00
- Desc:
- fixed broken model XML, changed documentation
- Permanent Source URI:
- https://models.cellml.org/workspace/faville_pullan_sanders_koh_lloyd_smith_2009/rawfile/44c711eaa446d3482e822ac8771da79db7c54309/faville_pacemaker_unit_2008.cellml
<?xml version="1.0" encoding="UTF-8"?>
<model
name="faville_pullan_sanders_koh_lloyd_smith_2009_pacemaker"
cmeta:id="faville_pullan_sanders_koh_lloyd_smith_2009_pacemaker"
xmlns="http://www.cellml.org/cellml/1.1#"
xmlns:cellml="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:dc="http://purl.org/dc/elements/1.1/"
xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
xmlns:bqs="http://www.cellml.org/bqs/1.0#"
xmlns:dcterms="http://purl.org/dc/terms/"
xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" >
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>A Biophysically-Based Mathematical Representation of Interstitial Cells of Cajal Pacemaker Potentials produced from a Unitary Potential
Basis</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML model describes the pacemaker unit of the Faville et al. 2008 model. This model is imported by the bulk cytoplasm model from the same publication 10 times. This CellML model is known to run PCEnv to replicate the published results. Because the model is in a CellML 1.1 format (as opposed to CellML 1.0) COR is unable to run the model.</para>
<para>ValidateCellML confirms this model as valid CellML. Unit checking was carried out where possible and to our knowledge they are consistent.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Phasic gastrointestinal (GI) muscle is able to autonomously generate rhythmic contractions independent of the enteric nervous system. The electrical activity that generates these rhythmic contractions are called slow waves, or pacemaker potentials (PP), and they are produced by a specialised group of pacemaker cells called Interstitial Cells of Cajal (ICC). They pass via gap junctions from the ICC to smooth muscle cells (SMC), activating L-type Ca2+ channels, Ca2+ influx and the contraction of the SMC. Full slow waves result from the summation of a large number of localised cellular membrane fluctuations, and are know as unitary potentials (UPs). These are generated at intracellular sites called pacemaker units, and are known to play an essential role in driving the coordinated contraction of GI muscles.
</para>
<para>
In the study described here, Richard Faville <emphasis>et al.</emphasis> have developed a mathematical model of the ICC pacemaker potential. The model can be divided into two distinct components: the bulk cytoplasm and the pacemaker units. The later have been described previously (Faville <emphasis>et al.</emphasis>, 2008, and the CellML description of this model can be found <ulink url="http://models.cellml.org/workspace/faville_pullan_sanders_koh_lloyd_smith_2009/@@file/a69dfff7b0d090bc51b49b5e4cda835130354d8d/faville_pacemaker_unit_2008.cellml">here</ulink>). The pacemaker unit model quantitatively describes the transmembrane ion flows and intracellular Ca2+ dynamics from a single ICC pacemaker unit, and a schematic diagram of this model can be seen in the figure immediately below.
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="faville_2008_new.png"/>
</imageobject>
</mediaobject>
<caption>A schematic diagram of the pacemaker unit illustrating all the compartmental volumes and ionic conductances, together with their interactions.</caption>
</informalfigure>
<para>
The bulk cytoplasmic model describes the ionic conductances that have been identified as being essential for the for coordinated ICC activity, but were absent in the pacemaker unit description, namely 2 calcium currents; I_CaT and I_Ca(Ext); several potassium currents; I_K(v1.1), I_K(ERG), I_K(Ca), and I_K(B); and finally, a non-specific inward leakage current (I_L). In addition, the bulk cytoplasmic model also describes intracellular calcium fluxes, and defines state variable derivatives such as the cytosolic calcium concentration (C_Cy), and the membrane potential (Vm).
</para>
<para>
The combined model is described here in CellML 1.1. The pacemaker unit is defined and is imported into the bulk cytoplasm 7 times (note that the number of pacemaker units that could be used within the modelling framework is completely arbitrary, however 7 appears to be the minimum number required to adequately describe the pacemaker potential depolarisation). In order to embed the pacemaker model within the bulk cytoplasm modelling framework the original pacemaker model had to be modified slightly. This is because the it was only representative of pacemaker activity near the resting membrane potential of -70mV. In its modified form and embedded within the bulk cytoplasm it is now capable of simulating pacemaker activity under conditions of membrane depolarisation (Vm > -60mV). A full schematic diagram of the combined model is illustrated in the figure below.
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="faville2_2008.png"/>
</imageobject>
</mediaobject>
<caption>A full schematic diagram of the bulk cytoplasm model with the imported pacemaker units illustrating all the compartmental volumes and ionic conductances, together with their interactions.</caption>
</informalfigure>
<!--
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://www.springerlink.com/content/652t4456624w2502/">A Biophysically Based Mathematical Model of Unitary Potential Activity in Interstitial Cells of Cajal</ulink>, R.A. Faville, A.J. Pullan, K.M. Sanders, and N.P. Smith, 2008, <ulink url="http://www.biophysj.org/">
<emphasis>Biophysical Journal</emphasis>
</ulink>. (A <ulink url="http://www.biophysj.org/cgi/rapidpdf/biophysj.107.122507v1">PDF</ulink> version of the article are available to journal subscribers on the <emphasis>Biophysical Journal</emphasis> website.) <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=18339738&query_hl=1&itool=pubmed_docsum">PubMed ID: 18339738</ulink>
</para>
-->
</sect1>
</article>
</documentation>
<cmeta:comment rdf:parseType="Resource">
<rdf:value>
This CellML model describes the pacemaker unit of the Faville et al. 2008 model. This model is imported by the bulk cytoplasm model from the same publication 10 times.
</rdf:value>
<dc:creator rdf:parseType="Resource">
<vCard:FN>Catherine Lloyd</vCard:FN>
</dc:creator>
</cmeta:comment>
<units name="millivolt">
<unit prefix="milli" units="volt" />
</units>
<units name="per_millivolt">
<unit units="millivolt" exponent="-1" />
</units>
<units name="per_second_per_millivolt">
<unit units="second" exponent="-1" />
<unit units="millivolt" exponent="-1" />
</units>
<units name="micromolar">
<unit prefix="micro" units="mole" />
<unit units="litre" exponent="-1" />
</units>
<units name="per_micromolar">
<unit units="micromolar" exponent="-1" />
</units>
<units name="per_micromolar2">
<unit units="micromolar" exponent="-2" />
</units>
<units name="picofarad">
<unit prefix="pico" units="farad" />
</units>
<units name="picosiemens">
<unit prefix="pico" units="siemens" />
</units>
<units name="picoampere">
<unit prefix="pico" units="ampere" />
</units>
<units name="femtoampere">
<unit prefix="femto" units="ampere" />
</units>
<units name="micromolar_per_coulomb">
<unit units="micromolar" />
<unit units="coulomb" exponent="-1" />
</units>
<units name="femtocoulomb_per_zeptomole">
<unit prefix="femto" units="coulomb" />
<unit prefix="zepto" units="mole" exponent="-1" />
</units>
<units name="attojoule_per_zeptomole_kelvin">
<unit prefix="atto" units="joule"/>
<unit prefix="zepto" units="mole" exponent="-1" />
<unit units="kelvin" exponent="-1" />
</units>
<units name="first_order_rate_constant">
<unit units="second" exponent="-1" />
</units>
<units name="per_second_squared">
<unit units="second" exponent="-2" />
</units>
<units name="flux">
<unit units="micromolar" />
<unit units="second" exponent="-1" />
</units>
<cmeta:comment rdf:parseType="Resource">
<rdf:value>
In order to facilitate the import of this pacemaker unit model by the bulk cytoplasm model I will encapsulate the current model in a top component called "pacemaker_unit_model".
</rdf:value>
<dc:creator rdf:parseType="Resource">
<vCard:FN>Catherine Lloyd</vCard:FN>
</dc:creator>
</cmeta:comment>
<component name="pacemaker_unit_model" cmeta:id="pacemaker_unit_model">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/0P/PP-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="pacemaker_unit_model">
<dc:title>pacemaker_unit_model</dc:title>
<dcterms:alternative>top component which encapsulates the entire pacemaker unit model</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="I_ion_PU" public_interface="out" private_interface="in" units="picoampere" />
<variable name="CS1" public_interface="out" private_interface="in" units="micromolar" />
<variable name="CS2" public_interface="out" private_interface="in" units="micromolar" />
<variable name="n_PU" public_interface="in" private_interface="out" units="dimensionless" />
<variable name="JS2Cy" public_interface="in" private_interface="out" units="flux" />
<variable name="JS1S2" public_interface="in" private_interface="out" units="flux" />
<variable name="Vm" public_interface="in" private_interface="out" units="millivolt" />
<variable name="time" public_interface="in" private_interface="out" units="second" />
</component>
<connection>
<map_components component_1="pacemaker_unit_model" component_2="PU_membrane" />
<map_variables variable_1="I_ion_PU" variable_2="I_ion_PU" />
</connection>
<connection>
<map_components component_1="pacemaker_unit_model" component_2="CS2" />
<map_variables variable_1="CS2" variable_2="CS2" />
<map_variables variable_1="time" variable_2="time" />
<map_variables variable_1="JS2Cy" variable_2="JS2Cy" />
<map_variables variable_1="JS1S2" variable_2="JS1S2" />
</connection>
<connection>
<map_components component_1="pacemaker_unit_model" component_2="CS1" />
<map_variables variable_1="CS1" variable_2="CS1" />
<map_variables variable_1="JS1S2" variable_2="JS1S2" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="pacemaker_unit_model" component_2="model_parameters" />
<map_variables variable_1="n_PU" variable_2="n_PU" />
</connection>
<connection>
<map_components component_1="pacemaker_unit_model" component_2="I_NaP" />
<map_variables variable_1="Vm" variable_2="Vm" />
</connection>
<connection>
<map_components component_1="pacemaker_unit_model" component_2="I_Na" />
<map_variables variable_1="Vm" variable_2="Vm" />
</connection>
<connection>
<map_components component_1="pacemaker_unit_model" component_2="I_Ca" />
<map_variables variable_1="Vm" variable_2="Vm" />
</connection>
<connection>
<map_components component_1="pacemaker_unit_model" component_2="I_NSCC_Ca" />
<map_variables variable_1="Vm" variable_2="Vm" />
</connection>
<connection>
<map_components component_1="pacemaker_unit_model" component_2="I_NSCC_Na" />
<map_variables variable_1="Vm" variable_2="Vm" />
</connection>
<connection>
<map_components component_1="pacemaker_unit_model" component_2="JIPR" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="pacemaker_unit_model" component_2="CER" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="pacemaker_unit_model" component_2="CMT" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="pacemaker_unit_model" component_2="NS1" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<cmeta:comment rdf:parseType="Resource">
<rdf:value>
Calcium flux which occurs between the pacemaker unit(s) and the bulk cytosol. The value of mu_S2Cy is imported from the "model_parameters" component of the main model.
</rdf:value>
<dc:creator rdf:parseType="Resource">
<vCard:FN>Catherine Lloyd</vCard:FN>
</dc:creator>
</cmeta:comment>
<cmeta:comment rdf:parseType="Resource">
<rdf:value>
Pacemaker unit equations.
</rdf:value>
<dc:creator rdf:parseType="Resource">
<vCard:FN>Catherine Lloyd</vCard:FN>
</dc:creator>
</cmeta:comment>
<component name="PU_membrane">
<variable name="I_iCa" public_interface="out" units="picoampere" />
<variable name="I_iNa" public_interface="out" units="picoampere" />
<variable name="I_ion_PU" public_interface="out" units="picoampere" />
<variable name="alpha_scale" public_interface="in" units="dimensionless" />
<variable name="I_Ca" public_interface="in" units="picoampere" />
<variable name="I_Na" public_interface="in" units="picoampere" />
<variable name="I_NaP" public_interface="in" units="picoampere" />
<variable name="I_NSCC_Ca" public_interface="in" units="picoampere" />
<variable name="I_PM" public_interface="in" units="picoampere" />
<variable name="I_NSCC_Na" public_interface="in" units="picoampere" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="1" >
<apply><eq />
<ci> I_iCa </ci>
<apply><times />
<ci> alpha_scale </ci>
<apply><plus />
<ci> I_Ca </ci>
<ci> I_NSCC_Ca </ci>
<ci> I_PM </ci>
</apply>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="2" >
<apply><eq />
<ci> I_iNa </ci>
<apply><times />
<ci> alpha_scale </ci>
<apply><plus />
<ci> I_NSCC_Na </ci>
<ci> I_Na </ci>
<ci> I_NaP </ci>
</apply>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="3" >
<apply><eq />
<ci> I_ion_PU </ci>
<apply><plus />
<ci> I_iCa </ci>
<ci> I_iNa </ci>
</apply>
</apply>
</math>
</component>
<component name="I_Ca" cmeta:id="I_Ca">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/0P/PP-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="I_Ca">
<dc:title>I_Ca</dc:title>
<dcterms:alternative>inward calcium current</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="I_Ca" public_interface="out" units="picoampere" />
<variable name="gCa_" initial_value="0.074" units="picosiemens" />
<variable name="kCa" initial_value="0.013" units="per_millivolt" />
<variable name="gCa" units="picosiemens" />
<variable name="ECa_PU" units="millivolt" />
<variable name="Vm" public_interface="in" units="millivolt" />
<variable name="T" public_interface="in" units="kelvin" />
<variable name="R" public_interface="in" units="attojoule_per_zeptomole_kelvin" />
<variable name="F" public_interface="in" units="femtocoulomb_per_zeptomole" />
<variable name="CO" public_interface="in" units="micromolar" />
<variable name="CS1" public_interface="in" units="micromolar" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="4">
<apply><eq />
<ci> I_Ca </ci>
<apply><times />
<ci> gCa </ci>
<apply><minus />
<ci> Vm </ci>
<ci> ECa_PU </ci>
</apply>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="5" >
<apply><eq />
<ci> gCa </ci>
<apply><times />
<ci> gCa_ </ci>
<apply><exp />
<apply><times />
<ci> kCa </ci>
<ci> Vm </ci>
</apply>
</apply>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="6" >
<apply><eq />
<ci> ECa_PU </ci>
<apply><times />
<apply><divide />
<apply><times />
<ci> R </ci>
<ci> T </ci>
</apply>
<apply><times />
<cn cellml:units="dimensionless"> 2.0 </cn>
<ci> F </ci>
</apply>
</apply>
<apply><ln />
<apply><divide />
<ci> CO </ci>
<ci> CS1 </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="I_NSCC_Ca" cmeta:id="I_NSCC_Ca">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/0P/PP-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="I_NSCC_Ca">
<dc:title>I_NSCC_Ca</dc:title>
<dcterms:alternative>non-selective calcium conductance</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="I_NSCC_Ca" public_interface="out" units="picoampere" />
<variable name="gNSCC_Ca_" initial_value="0.10" units="picosiemens" />
<variable name="gNSCC_Ca" units="picosiemens" />
<variable name="hNSCC" public_interface="in" units="dimensionless" />
<variable name="Vm" public_interface="in" units="millivolt" />
<variable name="ENSCC" public_interface="in" units="millivolt" />
<variable name="KNSCC" public_interface="in" units="micromolar" />
<variable name="CS1" public_interface="in" units="micromolar" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="7" >
<apply><eq />
<ci> gNSCC_Ca </ci>
<apply><times />
<ci> gNSCC_Ca_ </ci>
<apply><divide />
<apply><power />
<ci> KNSCC </ci>
<ci> hNSCC </ci>
</apply>
<apply><plus />
<apply><power />
<ci> KNSCC </ci>
<ci> hNSCC </ci>
</apply>
<apply><power />
<ci> CS1 </ci>
<ci> hNSCC </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="8" >
<apply><eq />
<ci> I_NSCC_Ca </ci>
<apply><times />
<ci> gNSCC_Ca </ci>
<apply><minus />
<ci> Vm </ci>
<ci> ENSCC </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="I_NSCC_Na" cmeta:id="I_NSCC_Na">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/0P/PP-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="I_NSCC_Na">
<dc:title>I_NSCC_Na</dc:title>
<dcterms:alternative>non-selective sodium conductance</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="I_NSCC_Na" public_interface="out" units="picoampere" />
<variable name="gNSCC_Na_" initial_value="160.0" units="picosiemens" />
<variable name="gNSCC_Na" units="picosiemens" />
<variable name="hNSCC" public_interface="in" units="dimensionless" />
<variable name="Vm" public_interface="in" units="millivolt" />
<variable name="ENSCC" public_interface="in" units="millivolt" />
<variable name="KNSCC" public_interface="in" units="micromolar" />
<variable name="CS1" public_interface="in" units="micromolar" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="9" >
<apply><eq />
<ci> gNSCC_Na </ci>
<apply><times />
<ci> gNSCC_Na_ </ci>
<apply><divide />
<apply><power />
<ci> KNSCC </ci>
<ci> hNSCC </ci>
</apply>
<apply><plus />
<apply><power />
<ci> KNSCC </ci>
<ci> hNSCC </ci>
</apply>
<apply><power />
<ci> CS1 </ci>
<ci> hNSCC </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="10" >
<apply><eq />
<ci> I_NSCC_Na </ci>
<apply><times />
<ci> gNSCC_Na </ci>
<apply><minus />
<ci> Vm </ci>
<ci> ENSCC </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="I_PM" cmeta:id="I_PM">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/0P/PP-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="I_PM">
<dc:title>I_PM</dc:title>
<dcterms:alternative>plasma membrane Ca2+-ATPase current</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="I_PM" public_interface="out" units="picoampere" />
<variable name="gPM" initial_value="675.0" units="femtoampere" />
<variable name="KPM" initial_value="1.0" units="micromolar" />
<variable name="CS1" public_interface="in" units="micromolar" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="11" >
<apply><eq />
<ci> I_PM </ci>
<apply><times />
<ci> gPM </ci>
<apply><divide />
<apply><power />
<ci> CS1 </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
<apply><plus />
<apply><power />
<ci> KPM </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
<apply><power />
<ci> CS1 </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="I_Na" cmeta:id="I_Na">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/0P/PP-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="I_Na">
<dc:title>I_Na</dc:title>
<dcterms:alternative>inward sodium current</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="I_Na" public_interface="out" units="picoampere" />
<variable name="gNa" initial_value="13.5" units="picosiemens" />
<variable name="ENa_PU" units="millivolt" />
<variable name="Vm" public_interface="in" units="millivolt" />
<variable name="T" public_interface="in" units="kelvin" />
<variable name="R" public_interface="in" units="attojoule_per_zeptomole_kelvin" />
<variable name="F" public_interface="in" units="femtocoulomb_per_zeptomole" />
<variable name="NO" public_interface="in" units="micromolar" />
<variable name="NS1" public_interface="in" units="micromolar" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="12" >
<apply><eq />
<ci> I_Na </ci>
<apply><times />
<ci> gNa </ci>
<apply><minus />
<ci> Vm </ci>
<ci> ENa_PU </ci>
</apply>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="13" >
<apply><eq />
<ci> ENa_PU </ci>
<apply><times />
<apply><divide />
<apply><times />
<ci> R </ci>
<ci> T </ci>
</apply>
<ci> F </ci>
</apply>
<apply><ln />
<apply><divide />
<ci> NO </ci>
<ci> NS1 </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="I_NaP" cmeta:id="I_NaP">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/0P/PP-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="I_NaP">
<dc:title>I_NaP</dc:title>
<dcterms:alternative>outward sodium pump</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="I_NaP" public_interface="out" units="picoampere" />
<variable name="gNaP" initial_value="187.5" units="picosiemens" />
<variable name="KNaP" initial_value="1.0E4" units="micromolar" />
<variable name="hNaP" initial_value="4.0" units="dimensionless" />
<variable name="ENaP" initial_value="10.0" units="millivolt" />
<variable name="NS1" public_interface="in" units="micromolar" />
<variable name="Vm" public_interface="in" units="millivolt" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="14">
<apply><eq />
<ci> I_NaP </ci>
<apply><times />
<ci> gNaP </ci>
<apply><divide />
<apply><power />
<ci> NS1 </ci>
<ci> hNaP </ci>
</apply>
<apply><plus />
<apply><power />
<ci> KNaP </ci>
<ci> hNaP </ci>
</apply>
<apply><power />
<ci> NS1 </ci>
<ci> hNaP </ci>
</apply>
</apply>
</apply>
<apply><minus />
<ci> ENaP </ci>
<ci> Vm </ci>
</apply>
</apply>
</apply>
</math>
</component>
<cmeta:comment rdf:parseType="Resource">
<rdf:value>
Calcium fluxes which occur within the pacemaker unit.
</rdf:value>
<dc:creator rdf:parseType="Resource">
<vCard:FN>Catherine Lloyd</vCard:FN>
</dc:creator>
</cmeta:comment>
<component name="JSERCA" cmeta:id="JSERCA">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/0P/PP-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="JSERCA">
<dc:title>JSERCA</dc:title>
<dcterms:alternative>SERCA pump</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="JSERCA" public_interface="out" units="flux" />
<variable name="VSERCA" initial_value="1.0E5" units="first_order_rate_constant" />
<variable name="A2" initial_value="6E-4" units="dimensionless" />
<variable name="A4" initial_value="3.57" units="per_micromolar" />
<variable name="A5" initial_value="2.7E-5" units="per_micromolar" />
<variable name="A6" initial_value="2.31E-5" units="per_micromolar2" />
<variable name="CER" public_interface="in" units="micromolar" />
<variable name="CS1" public_interface="in" units="micromolar" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="15">
<apply><eq />
<ci> JSERCA </ci>
<apply><divide />
<apply><times />
<ci> VSERCA </ci>
<apply><minus />
<ci> CS1 </ci>
<apply><times />
<ci> A2 </ci>
<ci> CER </ci>
</apply>
</apply>
</apply>
<apply><plus />
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply><times />
<ci> A4 </ci>
<ci> CS1 </ci>
</apply>
<apply><times />
<ci> A5 </ci>
<ci> CER </ci>
</apply>
<apply><times />
<ci> A6 </ci>
<ci> CS1 </ci>
<ci> CER </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="JMCU" cmeta:id="JMCU">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/0P/PP-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="JMCU">
<dc:title>JMCU</dc:title>
<dcterms:alternative>mitochondrial Ca2+ uniporter</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="JMCU" public_interface="out" units="flux" />
<variable name="VMCU" initial_value="800.0" units="flux" />
<variable name="KMCU" initial_value="10.0" units="micromolar" />
<variable name="epsilon_INH" units="dimensionless" />
<variable name="KINH" initial_value="10.0" units="micromolar" />
<variable name="hINH" initial_value="4.0" units="dimensionless" />
<variable name="CS2" public_interface="in" units="micromolar" />
<variable name="CMT" public_interface="in" units="micromolar" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="16">
<apply><eq />
<ci> JMCU </ci>
<apply><times />
<ci> VMCU </ci>
<apply><divide />
<apply><power />
<ci> CS2 </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
<apply><plus />
<apply><power />
<ci> KMCU </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
<apply><power />
<ci> CS2 </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
</apply>
<ci> epsilon_INH </ci>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="17" >
<apply><eq />
<ci> epsilon_INH </ci>
<apply><divide />
<apply><power />
<ci> KINH </ci>
<ci> hINH </ci>
</apply>
<apply><plus />
<apply><power />
<ci> KINH </ci>
<ci> hINH </ci>
</apply>
<apply><power />
<ci> CMT </ci>
<ci> hINH </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="JNCX" cmeta:id="JNCX">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/0P/PP-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="JNCX">
<dc:title>JNCX</dc:title>
<dcterms:alternative>mitochondrial Na+/Ca2+ exchanger</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="JNCX" public_interface="out" units="flux" />
<variable name="VNCX" initial_value="3.0" units="flux" />
<variable name="KNCX" initial_value="0.3" units="micromolar" />
<variable name="CMT" public_interface="in" units="micromolar" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="18">
<apply><eq />
<ci> JNCX </ci>
<apply><times />
<ci> VNCX </ci>
<apply><divide />
<ci> CMT </ci>
<apply><plus />
<ci> CMT </ci>
<ci> KNCX </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="JIPR" cmeta:id="JIPR">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/0P/PP-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="JIPR">
<dc:title>JIPR</dc:title>
<dcterms:alternative>IP3R Ca2+ flux</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="JIPR" public_interface="out" units="flux" />
<variable name="kIPR" initial_value="2000.0" units="first_order_rate_constant" />
<variable name="k_1" initial_value="6.4" units="flux" />
<variable name="k1" initial_value="0.0" units="first_order_rate_constant" />
<variable name="k2" initial_value="4.0" units="first_order_rate_constant" />
<variable name="r2" initial_value="250.0" units="first_order_rate_constant" />
<variable name="r_2" initial_value="0.0" units="flux" />
<variable name="r4" initial_value="750.0" units="first_order_rate_constant" />
<variable name="R1" initial_value="36.0" units="micromolar" />
<variable name="R3" initial_value="300.0" units="micromolar" />
<variable name="phi1" units="first_order_rate_constant" />
<variable name="phi_1" units="flux" />
<variable name="phi2" units="first_order_rate_constant" />
<variable name="phi3" units="first_order_rate_constant" />
<variable name="H" initial_value="0.200" units="dimensionless" />
<variable name="g_beta" initial_value="1500.0" units="first_order_rate_constant" />
<variable name="h_beta" initial_value="4.0" units="dimensionless" />
<variable name="g_alpha" initial_value="0.85" units="first_order_rate_constant" />
<variable name="K_beta" initial_value="0.35" units="micromolar" />
<variable name="alpha_zeta" units="first_order_rate_constant" />
<variable name="beta_zeta" units="first_order_rate_constant" />
<variable name="zeta" initial_value="0.300" units="dimensionless" />
<variable name="K_phi3_act" initial_value="0.1" units="micromolar" />
<variable name="K_phi3_inh" initial_value="0.5" units="micromolar" />
<variable name="h_phi3_act" initial_value="3.0" units="dimensionless" />
<variable name="h_phi3_inh" initial_value="3.0" units="dimensionless" />
<variable name="g_phi3" initial_value="4.5" units="first_order_rate_constant" />
<variable name="CER" public_interface="in" units="micromolar" />
<variable name="CS2" public_interface="in" units="micromolar" />
<variable name="P" public_interface="in" units="micromolar" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="19">
<apply><eq />
<apply><diff />
<bvar><ci>time</ci></bvar>
<ci> H </ci>
</apply>
<apply><minus />
<apply><times />
<ci> phi3 </ci>
<apply><minus />
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> H </ci>
</apply>
</apply>
<apply><times />
<apply><divide />
<apply><times />
<ci> P </ci>
<ci> phi1 </ci>
<ci> phi2 </ci>
</apply>
<apply><plus />
<apply><times />
<ci> P </ci>
<ci> phi1 </ci>
</apply>
<ci> phi_1 </ci>
</apply>
</apply>
<ci> H </ci>
</apply>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="20" >
<apply><eq />
<ci> JIPR </ci>
<apply><times />
<ci> kIPR </ci>
<apply><power />
<apply><divide />
<apply><times />
<ci> P </ci>
<ci> phi1 </ci>
<ci> H </ci>
</apply>
<apply><plus />
<apply><times />
<ci> P </ci>
<ci> phi1 </ci>
</apply>
<ci> phi_1 </ci>
</apply>
</apply>
<cn cellml:units="dimensionless"> 4.0 </cn>
</apply>
<apply><minus />
<ci> CER </ci>
<ci> CS2 </ci>
</apply>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="21" >
<apply><eq />
<ci> phi1 </ci>
<apply><divide />
<apply><plus />
<apply><times />
<ci> k1 </ci>
<ci> R1 </ci>
</apply>
<apply><times />
<ci> r2 </ci>
<ci> CS2 </ci>
</apply>
</apply>
<apply><plus />
<ci> R1 </ci>
<ci> CS2 </ci>
</apply>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="22" >
<apply><eq />
<ci> phi_1 </ci>
<apply><divide />
<apply><times />
<apply><plus />
<ci> k_1 </ci>
<ci> r_2 </ci>
</apply>
<ci> R3 </ci>
</apply>
<apply><plus />
<ci> R3 </ci>
<ci> CS2 </ci>
</apply>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="23" >
<apply><eq />
<ci> phi2 </ci>
<apply><divide />
<apply><plus />
<apply><times />
<ci> k2 </ci>
<ci> R3 </ci>
</apply>
<apply><times />
<ci> r4 </ci>
<ci> CS2 </ci>
</apply>
</apply>
<apply><plus />
<ci> R3 </ci>
<ci> CS2 </ci>
</apply>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="24" >
<apply><eq />
<ci> phi3 </ci>
<apply><divide />
<apply><times />
<ci> g_phi3 </ci>
<ci> zeta </ci>
</apply>
<apply><times />
<apply><plus />
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply><power />
<apply><divide />
<ci> K_phi3_act </ci>
<ci> CS2 </ci>
</apply>
<ci> h_phi3_act </ci>
</apply>
</apply>
<apply><plus />
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply><power />
<apply><divide />
<ci> CS2 </ci>
<ci> K_phi3_inh </ci>
</apply>
<ci> h_phi3_inh </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="25" >
<apply><eq />
<ci> alpha_zeta </ci>
<ci> g_alpha </ci>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="26" >
<apply><eq />
<ci> beta_zeta </ci>
<apply><divide />
<ci> g_beta </ci>
<apply><plus />
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply><power />
<apply><divide />
<ci> K_beta </ci>
<ci> CS2 </ci>
</apply>
<ci> h_beta </ci>
</apply>
</apply>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="27" >
<apply><eq />
<apply><diff />
<bvar><ci>time</ci></bvar>
<ci> zeta </ci>
</apply>
<apply><minus />
<apply><times />
<ci> alpha_zeta </ci>
<apply><minus />
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> zeta </ci>
</apply>
</apply>
<apply><times />
<ci> beta_zeta </ci>
<ci> zeta </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="CS1" cmeta:id="CS1">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/0P/PP-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="CS1">
<dc:title>CS1</dc:title>
<dcterms:alternative>calcium concentration in cytoplasmic subspace 1</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="CS1" initial_value="0.120" public_interface="out" units="micromolar" />
<variable name="lambda_MT_S1" units="dimensionless" />
<variable name="lambda_ER_S1" units="dimensionless" />
<variable name="JS1S2" public_interface="in" units="flux" />
<variable name="JNCX" public_interface="in" units="flux" />
<variable name="JSERCA" public_interface="in" units="flux" />
<variable name="I_iCa" public_interface="in" units="picoampere" />
<variable name="delta_SPU" public_interface="in" units="micromolar_per_coulomb" />
<variable name="gamma_S1" public_interface="in" units="dimensionless" />
<variable name="gamma_MT" public_interface="in" units="dimensionless" />
<variable name="gamma_ER" public_interface="in" units="dimensionless" />
<variable name="alpha_scale" public_interface="in" units="dimensionless" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="28">
<apply><eq />
<apply><diff />
<bvar><ci>time</ci></bvar>
<ci> CS1 </ci>
</apply>
<apply><minus />
<apply><plus />
<ci> JS1S2 </ci>
<apply><times />
<ci> lambda_MT_S1 </ci>
<ci> JNCX </ci>
</apply>
</apply>
<apply><plus />
<apply><times />
<apply><divide />
<ci> delta_SPU </ci>
<apply><times />
<ci> alpha_scale </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
<ci> I_iCa </ci>
</apply>
<apply><times />
<ci> lambda_ER_S1 </ci>
<ci> JSERCA </ci>
</apply>
</apply>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="29" >
<apply><eq />
<ci> lambda_MT_S1 </ci>
<apply><divide />
<ci> gamma_MT </ci>
<ci> gamma_S1 </ci>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="30" >
<apply><eq />
<ci> lambda_ER_S1 </ci>
<apply><divide />
<ci> gamma_ER </ci>
<ci> gamma_S1 </ci>
</apply>
</apply>
</math>
</component>
<component name="CS2" cmeta:id="CS2">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/0P/PP-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="CS2">
<dc:title>CS2</dc:title>
<dcterms:alternative>calcium concentration in cytoplasmic subspace 2</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="CS2" initial_value="0.023" public_interface="out" units="micromolar" />
<variable name="lambda_MT_S2" units="dimensionless" />
<variable name="lambda_ER_S2" units="dimensionless" />
<variable name="lambda_S1_S2" units="dimensionless" />
<variable name="JS1S2" public_interface="in" units="flux" />
<variable name="JS2Cy" public_interface="in" units="flux" />
<variable name="JMCU" public_interface="in" units="flux" />
<variable name="JIPR" public_interface="in" units="flux" />
<variable name="gamma_S1" public_interface="in" units="dimensionless" />
<variable name="gamma_S2" public_interface="in" units="dimensionless" />
<variable name="gamma_MT" public_interface="in" units="dimensionless" />
<variable name="gamma_ER" public_interface="in" units="dimensionless" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="31">
<apply><eq />
<apply><diff />
<bvar><ci>time</ci></bvar>
<ci> CS2 </ci>
</apply>
<apply><minus />
<apply><plus />
<ci> JS2Cy </ci>
<apply><times />
<ci> lambda_ER_S2 </ci>
<ci> JIPR </ci>
</apply>
</apply>
<apply><plus />
<apply><times />
<ci> lambda_S1_S2 </ci>
<ci> JS1S2 </ci>
</apply>
<apply><times />
<ci> lambda_MT_S2 </ci>
<ci> JMCU </ci>
</apply>
</apply>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="32" >
<apply><eq />
<ci> lambda_MT_S2 </ci>
<apply><divide />
<ci> gamma_MT </ci>
<ci> gamma_S2 </ci>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="33" >
<apply><eq />
<ci> lambda_ER_S2 </ci>
<apply><divide />
<ci> gamma_ER </ci>
<ci> gamma_S2 </ci>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="34" >
<apply><eq />
<ci> lambda_S1_S2 </ci>
<apply><divide />
<ci> gamma_S1 </ci>
<ci> gamma_S2 </ci>
</apply>
</apply>
</math>
</component>
<component name="CER" cmeta:id="CER">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/0P/PP-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="CER">
<dc:title>CER</dc:title>
<dcterms:alternative>calcium concentration in the endoplasmic reticulum</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="CER" initial_value="200.0" public_interface="out" units="micromolar" />
<variable name="JSERCA" public_interface="in" units="flux" />
<variable name="JIPR" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="35">
<apply><eq />
<apply><diff />
<bvar><ci>time</ci></bvar>
<ci> CER </ci>
</apply>
<apply><minus />
<ci> JSERCA </ci>
<ci> JIPR </ci>
</apply>
</apply>
</math>
</component>
<component name="CMT" cmeta:id="CMT">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/0P/PP-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="CMT">
<dc:title>CMT</dc:title>
<dcterms:alternative>calcium concentration in the mitochondria</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="CMT" initial_value="0.200" public_interface="out" units="micromolar" />
<variable name="fm" units="dimensionless" />
<variable name="Km" initial_value="0.01" units="micromolar" />
<variable name="Bm" initial_value="100.0" units="micromolar" />
<variable name="JMCU" public_interface="in" units="flux" />
<variable name="JNCX" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="36">
<apply><eq />
<apply><diff />
<bvar><ci>time</ci></bvar>
<ci> CMT </ci>
</apply>
<apply><times />
<ci> fm </ci>
<apply><minus />
<ci> JMCU </ci>
<ci> JNCX </ci>
</apply>
</apply>
</apply>
</math>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="37" >
<apply><eq />
<ci> fm </ci>
<apply><divide />
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply><plus />
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply><divide />
<apply><times />
<ci> Km </ci>
<ci> Bm </ci>
</apply>
<apply><power />
<apply><plus />
<ci> Km </ci>
<ci> CMT </ci>
</apply>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="NS1" cmeta:id="NS1">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/0P/PP-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="NS1">
<dc:title>NS1</dc:title>
<dcterms:alternative>sodium concentration in cytoplasmic subspace 1</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="NS1" initial_value="1.01E4" public_interface="out" units="micromolar" />
<variable name="alpha_scale" public_interface="in" units="dimensionless" />
<variable name="delta_SPU" public_interface="in" units="micromolar_per_coulomb" />
<variable name="I_iNa" public_interface="in" units="picoampere" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="38">
<apply><eq />
<apply><diff />
<bvar><ci>time</ci></bvar>
<ci> NS1 </ci>
</apply>
<apply><times />
<apply><minus />
<apply><divide />
<ci> delta_SPU </ci>
<apply><times />
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> alpha_scale </ci>
</apply>
</apply>
</apply>
<ci> I_iNa </ci>
</apply>
</apply>
</math>
</component>
<component name="model_parameters">
<variable name="R" public_interface="out" initial_value="8.314E-3" units="attojoule_per_zeptomole_kelvin" />
<variable name="F" public_interface="out" initial_value="0.09649" units="femtocoulomb_per_zeptomole" />
<variable name="T" public_interface="out" initial_value="310.16" units="kelvin" />
<variable name="NO" public_interface="out" initial_value="140.0E3" units="micromolar" />
<variable name="CO" public_interface="out" initial_value="1.8E3" units="micromolar" />
<variable name="KO" public_interface="out" initial_value="5400.0" units="micromolar" />
<variable name="Ki" public_interface="out" initial_value="145E3" units="micromolar" />
<variable name="P" public_interface="out" initial_value="1.0" units="micromolar" />
<variable name="delta_SPU" public_interface="out" initial_value="18.5" units="micromolar_per_coulomb" />
<variable name="gamma_S1" public_interface="out" initial_value="100.0" units="dimensionless" />
<variable name="gamma_S2" public_interface="out" initial_value="1.0" units="dimensionless" />
<variable name="gamma_MT" public_interface="out" initial_value="200.0" units="dimensionless" />
<variable name="gamma_ER" public_interface="out" initial_value="20.0" units="dimensionless" />
<variable name="KNSCC" public_interface="out" initial_value="0.12" units="micromolar" />
<variable name="ENSCC" public_interface="out" initial_value="0.0" units="millivolt" />
<variable name="hNSCC" public_interface="out" initial_value="3.0" units="dimensionless" />
<variable name="alpha_scale" public_interface="out" units="dimensionless" />
<variable name="n_PU" public_interface="in" units="dimensionless" />
<variable name="n_PU_base" initial_value="50.0" units="dimensionless" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="39">
<apply><eq />
<ci> alpha_scale </ci>
<apply><divide />
<ci> n_PU_base </ci>
<ci> n_PU </ci>
</apply>
</apply>
</math>
</component>
<group>
<relationship_ref relationship="encapsulation" />
<component_ref component="pacemaker_unit_model">
<component_ref component="PU_membrane" />
<component_ref component="I_Ca" />
<component_ref component="I_Na" />
<component_ref component="I_NSCC_Ca" />
<component_ref component="I_NSCC_Na" />
<component_ref component="I_PM" />
<component_ref component="I_NaP" />
<component_ref component="JSERCA" />
<component_ref component="JMCU" />
<component_ref component="JIPR" />
<component_ref component="JNCX" />
<component_ref component="CS1" />
<component_ref component="CS2" />
<component_ref component="CER" />
<component_ref component="CMT" />
<component_ref component="NS1" />
<component_ref component="model_parameters" />
</component_ref>
</group>
<connection>
<map_components component_1="PU_membrane" component_2="I_Ca"/>
<map_variables variable_1="I_Ca" variable_2="I_Ca"/>
</connection>
<connection>
<map_components component_1="PU_membrane" component_2="I_NaP"/>
<map_variables variable_1="I_NaP" variable_2="I_NaP"/>
</connection>
<connection>
<map_components component_1="PU_membrane" component_2="I_Na"/>
<map_variables variable_1="I_Na" variable_2="I_Na"/>
</connection>
<connection>
<map_components component_1="PU_membrane" component_2="I_NSCC_Na"/>
<map_variables variable_1="I_NSCC_Na" variable_2="I_NSCC_Na"/>
</connection>
<connection>
<map_components component_1="PU_membrane" component_2="I_NSCC_Ca"/>
<map_variables variable_1="I_NSCC_Ca" variable_2="I_NSCC_Ca"/>
</connection>
<connection>
<map_components component_1="PU_membrane" component_2="I_PM"/>
<map_variables variable_1="I_PM" variable_2="I_PM"/>
</connection>
<connection>
<map_components component_1="PU_membrane" component_2="CS1"/>
<map_variables variable_1="I_iCa" variable_2="I_iCa"/>
</connection>
<connection>
<map_components component_1="PU_membrane" component_2="NS1"/>
<map_variables variable_1="I_iNa" variable_2="I_iNa"/>
</connection>
<connection>
<map_components component_1="PU_membrane" component_2="model_parameters"/>
<map_variables variable_1="alpha_scale" variable_2="alpha_scale" />
</connection>
<connection>
<map_components component_1="JSERCA" component_2="CS1" />
<map_variables variable_1="CS1" variable_2="CS1" />
<map_variables variable_1="JSERCA" variable_2="JSERCA" />
</connection>
<connection>
<map_components component_1="JNCX" component_2="CS1" />
<map_variables variable_1="JNCX" variable_2="JNCX" />
</connection>
<connection>
<map_components component_1="I_PM" component_2="CS1" />
<map_variables variable_1="CS1" variable_2="CS1" />
</connection>
<connection>
<map_components component_1="I_NSCC_Ca" component_2="CS1" />
<map_variables variable_1="CS1" variable_2="CS1" />
</connection>
<connection>
<map_components component_1="I_NSCC_Na" component_2="CS1" />
<map_variables variable_1="CS1" variable_2="CS1" />
</connection>
<connection>
<map_components component_1="model_parameters" component_2="CS1" />
<map_variables variable_1="delta_SPU" variable_2="delta_SPU" />
<map_variables variable_1="gamma_MT" variable_2="gamma_MT" />
<map_variables variable_1="gamma_S1" variable_2="gamma_S1" />
<map_variables variable_1="gamma_ER" variable_2="gamma_ER" />
<map_variables variable_1="alpha_scale" variable_2="alpha_scale" />
</connection>
<connection>
<map_components component_1="JMCU" component_2="CS2" />
<map_variables variable_1="CS2" variable_2="CS2" />
<map_variables variable_1="JMCU" variable_2="JMCU" />
</connection>
<connection>
<map_components component_1="JIPR" component_2="CS2" />
<map_variables variable_1="CS2" variable_2="CS2" />
<map_variables variable_1="JIPR" variable_2="JIPR" />
</connection>
<connection>
<map_components component_1="JIPR" component_2="model_parameters" />
<map_variables variable_1="P" variable_2="P" />
</connection>
<connection>
<map_components component_1="model_parameters" component_2="CS2" />
<map_variables variable_1="gamma_MT" variable_2="gamma_MT" />
<map_variables variable_1="gamma_S1" variable_2="gamma_S1" />
<map_variables variable_1="gamma_S2" variable_2="gamma_S2" />
<map_variables variable_1="gamma_ER" variable_2="gamma_ER" />
</connection>
<connection>
<map_components component_1="JSERCA" component_2="CER" />
<map_variables variable_1="CER" variable_2="CER" />
<map_variables variable_1="JSERCA" variable_2="JSERCA" />
</connection>
<connection>
<map_components component_1="JIPR" component_2="CER" />
<map_variables variable_1="CER" variable_2="CER" />
<map_variables variable_1="JIPR" variable_2="JIPR" />
</connection>
<connection>
<map_components component_1="JNCX" component_2="CMT" />
<map_variables variable_1="CMT" variable_2="CMT" />
<map_variables variable_1="JNCX" variable_2="JNCX" />
</connection>
<connection>
<map_components component_1="JMCU" component_2="CMT" />
<map_variables variable_1="CMT" variable_2="CMT" />
<map_variables variable_1="JMCU" variable_2="JMCU" />
</connection>
<connection>
<map_components component_1="model_parameters" component_2="NS1" />
<map_variables variable_1="delta_SPU" variable_2="delta_SPU" />
<map_variables variable_1="alpha_scale" variable_2="alpha_scale" />
</connection>
<connection>
<map_components component_1="model_parameters" component_2="I_NSCC_Ca" />
<map_variables variable_1="hNSCC" variable_2="hNSCC" />
<map_variables variable_1="ENSCC" variable_2="ENSCC" />
<map_variables variable_1="KNSCC" variable_2="KNSCC" />
</connection>
<connection>
<map_components component_1="model_parameters" component_2="I_NSCC_Na" />
<map_variables variable_1="hNSCC" variable_2="hNSCC" />
<map_variables variable_1="ENSCC" variable_2="ENSCC" />
<map_variables variable_1="KNSCC" variable_2="KNSCC" />
</connection>
<connection>
<map_components component_1="I_Ca" component_2="CS1" />
<map_variables variable_1="CS1" variable_2="CS1" />
</connection>
<connection>
<map_components component_1="I_Ca" component_2="model_parameters"/>
<map_variables variable_1="R" variable_2="R" />
<map_variables variable_1="T" variable_2="T" />
<map_variables variable_1="F" variable_2="F" />
<map_variables variable_1="CO" variable_2="CO" />
</connection>
<connection>
<map_components component_1="I_Na" component_2="model_parameters"/>
<map_variables variable_1="R" variable_2="R" />
<map_variables variable_1="T" variable_2="T" />
<map_variables variable_1="F" variable_2="F" />
<map_variables variable_1="NO" variable_2="NO" />
</connection>
<connection>
<map_components component_1="I_NaP" component_2="NS1" />
<map_variables variable_1="NS1" variable_2="NS1" />
</connection>
<connection>
<map_components component_1="I_Na" component_2="NS1" />
<map_variables variable_1="NS1" variable_2="NS1" />
</connection>
</model>
