<?xml version="1.0"?>

<!--  FILE :  rice_model2_2000_1_1_raw.xml

CREATED :  17th September 2003

LAST MODIFIED : 17th September 2003

AUTHOR :  Catherine Lloyd
          The Bioengineering Institute
          The University of Auckland
          
MODEL STATUS :  This model conforms to the CellML 1.1 Specification and the 
               16/01/2002 CellML Metadata 1.0 Specification.

DESCRIPTION :  This file contains a CellML description of Rice et al's 2000
               detailed model of ventricular cardiac myocytes.  It simulates
               action potentials, Ca2+-handling mechanisms and isometric force
               generation by the myofilaments.  Using the import and reuse 
               features of CellML 1.1 we embed these new mechanics within a 
               previously published ventricular myocyte model.

CHANGES:  
   
-->


<model
    
name="rice_model2_1_1_2000"
    
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">
  
<rdf:RDF xmlns:rdf="http://www.w3.org/2000/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.1#" 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>The 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>2003-09-17</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.
      -->

      
      
<!-- The Publisher metadata. -->
      
<dc:publisher>
        The University of Auckland, Bioengineering Institute
      
</dc:publisher>
    
</rdf:Description>
    
    
<!--
      The following metadata refers to the model itself, as indicated by the
      reference to the ID "rice_model2_2000", which is declared on the  
      <model> element.
    -->

    
<rdf:Description rdf:about="#rice_model2_2000">
      
<!-- A human readable name for the model. -->
      
<dc:title>
        Rice et al's 2000 detailed model of ventricular cardiac 
        myocytes
      
</dc:title>
      
      
<!-- A comment regarding the model. -->
      
<cmeta:comment rdf:parseType="Resource">
        
<rdf:value>
          This is the CellML description of Rice et al's 2000 detailed model of 
          ventricular cardiac myocytes.  It simulates action potentials, 
          Ca2+-handling mechanisms and isometric force generation by the 
          myofilaments.  Using the import and reuse features of CellML 1.1 we 
          embed these new mechanics within a previously published ventricular 
          myocyte model.
        
</rdf:value>
        
<!-- The creator of the comment. -->
        
<dc:creator rdf:parseType="Resource">
          
<vCard:FN>Catherine Lloyd</vCard:FN>
        
</dc:creator>
      
</cmeta:comment>
      
      
<!--  This model is specific to cardiac muscle. -->
      
<cmeta:bio_entity>Cardiac Myocyte</cmeta:bio_entity>
      
      
<!-- 
        The CellML Metadata Specification recommends that bibliographic metadata
        is used to provide information about the original model reference.  The 
        "identifier" attribute on the "BibliographicReference" class provides an
        elegant way to identify a cited reference using a database identifier   
        such as Pubmed.  All associated data such as author, journal title,     
        date, etc can be looked up on the database.
      -->

      
<bqs:reference rdf:parseType="Resource">
        
<bqs:Pubmed_id>10710361</bqs:Pubmed_id>
        
<bqs:JournalArticle rdf:parseType="Resource">
          
<dc:creator>
            
<rdf:Seq>
              
<rdf:li rdf:parseType="Resource">
                
<bqs:Person rdf:parseType="Resource">
                  
<vCard:N rdf:parseType="Resource">
                    
<vCard:Family>Rice</vCard:Family>
                    
<vCard:Given>John</vCard:Given>
                    
<vCard:Other>Jeremy</vCard:Other>
                  
</vCard:N>
                
</bqs:Person>
              
</rdf:li>
              
<rdf:li rdf:parseType="Resource">
                
<bqs:Person rdf:parseType="Resource">
                  
<vCard:N rdf:parseType="Resource">
                    
<vCard:Family>Jafri</vCard:Family>
                    
<vCard:Given>M</vCard:Given>
                    
<vCard:Other>Saleet</vCard:Other>
                  
</vCard:N>
                
</bqs:Person>
              
</rdf:li>
              
<rdf:li rdf:parseType="Resource">
                
<bqs:Person rdf:parseType="Resource">
                  
<vCard:N rdf:parseType="Resource">
                    
<vCard:Family>Winslow</vCard:Family>
                    
<vCard:Given>Raimond</vCard:Given>
                    
<vCard:Other>L</vCard:Other>
                  
</vCard:N>
                
</bqs:Person>
              
</rdf:li>
            
</rdf:Seq>
          
</dc:creator>
          
<dc:title>
            Modeling short-term interval-force relations in cardiac muscle
          
</dc:title>
          
<dcterms:issued rdf:parseType="Resource">
            
<dcterms:W3CDTF>2000-03</dcterms:W3CDTF>
          
</dcterms:issued>
          
<bqs:Journal rdf:parseType="Resource">
            
<dc:title>
              American Journal of Physiology:  Heart and Circulatory Physiology
            
</dc:title>
          
</bqs:Journal>
          
<bqs:volume>278</bqs:volume>
          
<bqs:first_page>H913</bqs:first_page>
          
<bqs:last_page>H931</bqs:last_page>
        
</bqs:JournalArticle>
      
</bqs:reference>
    
</rdf:Description>
  
</rdf:RDF>
  
  
<import xlink:href="http://www.cellml.org/examples/models/jafri_rice_winslow_model_1998.xml">
    
<units name="millisecond" units_ref="millisecond" />
    
<units name="per_millisecond" units_ref="per_millisecond" />
    
<units name="per_second" units_ref="per_second" />
    
<units name="millivolt" units_ref="millivolt" />
    
<units name="cm2" units_ref="cm2" />
    
<units name="micro_litre" units_ref="micro_litre" />
    
<units name="millimolar" units_ref="millimolar" />
    
<units name="micromolar" units_ref="micromolar" />
    
<units name="micromolar_per_second" units_ref="micromolar_per_second" />
    
<units name="micromolar_per_millisecond" units_ref="micromolar_per_millisecond" />
    
<units name="per_micromolar_per_second" units_ref="per_micromolar_per_second" />
    
<units name="per_micromolar3_per_millisecond" units_ref="per_micromolar3_per_millisecond" />
    
<units name="per_micromolar4_per_millisecond" units_ref="per_micromolar4_per_millisecond" />
    
<units name="microA_per_microF" units_ref="microA_per_microF" />
    
<units name="coulomb_per_millimole" units_ref="coulomb_per_millimole" />
    
    
<component name="environment" component_ref="environment" />
    
<component name="membrane" component_ref="membrane" />
    
<component name="fast_sodium_current" component_ref="fast_sodium_current" />
    
<component name="L_type_Ca_channel" component_ref="L_type_Ca_channel" />
    
<component name="time_dependent_potassium_current" component_ref="time_dependent_potassium_current" />
    
<component name="Na_Ca_exchanger" component_ref="Na_Ca_exchanger" />
    
<component name="time_independent_potassium_current" component_ref="time_independent_potassium_current" />
    
<component name="plateau_potassium_current" component_ref="plateau_potassium_current" />
    
<component name="sarcolemmal_calcium_pump" component_ref="sarcolemmal_calcium_pump" />
    
<component name="sodium_background_current" component_ref="sodium_background_current" />
    
<component name="calcium_background_current" component_ref="calcium_background_current" />
    
<component name="sodium_potassium_pump" component_ref="sodium_potassium_pump" />
    
<component name="non_specific_calcium_activated_current" component_ref="non_specific_calcium_activated_current" />
  
</import> 
  
  
<!-- Below, we define some additional units.  -->
  
  
<units name="micrometre">
    
<unit prefix="micro" units="metre" />
  
</units>
  
  
<units name="N_per_mm2">
    
<unit units="newton" />
    
<unit prefix="milli" units="metre" exponent="-2" />
  
</units>
  
  
<!-- New Components.  -->
  
  
<component name="cell_geometry">
    
<variable name="A_cap" public_interface="out" initial_value="1.534E-4" units="cm2" />
    
<variable name="V_myo" public_interface="out" initial_value="25.84E-6" units="micro_litre" />
    
<variable name="V_JSR" public_interface="out" initial_value="0.16E-6" units="micro_litre" />
    
<variable name="V_NSR" public_interface="out" initial_value="1.40E-6" units="micro_litre" />
    
<variable name="V_SS" public_interface="out" initial_value="0.495E-6" units="micro_litre" />
  
</component>
  
  
<component name="RyR_channel_states">
    
<variable name="P_O1" public_interface="out" initial_value="0.428917E-3" units="dimensionless" />
    
<variable name="P_O2" public_interface="out" initial_value="0.487455E-9" units="dimensionless" />
    
    
<variable name="P_C1" initial_value="0.637931" units="dimensionless" />
    
<variable name="P_C2" initial_value="0.361643" units="dimensionless" />
    
<variable name="k_a_plus" initial_value="0.01215" units="per_micromolar4_per_millisecond" />
    
<variable name="k_a_minus" initial_value="0.1425" units="per_millisecond" />
    
<variable name="k_b_plus" initial_value="0.00405" units="per_micromolar3_per_millisecond" />
    
<variable name="k_b_minus" initial_value="1.930" units="per_millisecond" />
    
<variable name="k_c_plus" initial_value="0.010" units="per_millisecond" />
    
<variable name="k_c_minus" initial_value="0.0008" units="per_millisecond" />
    
<variable name="n" initial_value="4.0" units="dimensionless" />
    
<variable name="m" initial_value="3.0" units="dimensionless" />
    
    
<variable name="time" public_interface="in" units="millisecond" />
    
<variable name="Ca_SS" public_interface="in" units="millimolar" />
    
    
<math xmlns="http://www.w3.org/1998/Math/MathML">
      
<apply id="P_C1_diff_eq"><eq />
        
<apply><diff />
          
<bvar><ci> time </ci></bvar>
          
<ci> P_C1 </ci>
        
</apply>
        
<apply><plus />
          
<apply><times />
            
<apply><minus />
              
<ci> k_a_plus </ci>
            
</apply>
            
<apply><power />
              
<ci> Ca_SS </ci>
              
<ci> n </ci>
            
</apply>
            
<ci> P_C1 </ci>
          
</apply>
          
<apply><times />
            
<ci> k_a_minus </ci>
            
<ci> P_O1 </ci>
          
</apply>
        
</apply>
      
</apply>
      
      
<apply id="P_O1_diff_eq"><eq />
        
<apply><diff />
          
<bvar><ci> time </ci></bvar>
          
<ci> P_O1 </ci>
        
</apply>
        
<apply><plus />
          
<apply><minus />
            
<apply><times />
              
<ci> k_a_plus </ci>
              
<apply><power />
                
<ci> Ca_SS </ci>
                
<ci> n </ci>
              
</apply>
              
<ci> P_C1 </ci>
            
</apply>
            
<apply><plus />
              
<apply><times />
                
<ci> k_a_minus </ci>
                
<ci> P_O1 </ci>
              
</apply>
              
<apply><times />
                
<ci> k_b_plus </ci>
                
<apply><power />
                  
<ci> Ca_SS </ci>
                  
<ci> m </ci>
                
</apply>
                
<ci> P_O1 </ci>
              
</apply>
              
<apply><times />
                
<ci> k_c_plus </ci>
                
<ci> P_O1 </ci>
              
</apply>
            
</apply>
          
</apply>
          
<apply><times />
            
<ci> k_b_minus </ci>
            
<ci> P_O2 </ci>
          
</apply>
          
<apply><times />
            
<ci> k_c_minus </ci>
            
<ci> P_C2 </ci>
          
</apply>
        
</apply>
      
</apply>
      
      
<apply id="P_O2_diff_eq"><eq />
        
<apply><diff />
          
<bvar><ci> time </ci></bvar>
          
<ci> P_O2 </ci>
        
</apply>
        
<apply><minus />
          
<apply><times />
            
<ci> k_b_plus </ci>
            
<apply><power />
              
<ci> Ca_SS </ci>
              
<ci> m </ci>
            
</apply>
            
<ci> P_O1 </ci>
          
</apply>
          
<apply><times />
            
<ci> k_b_minus </ci>
            
<ci> P_O2 </ci>
          
</apply>
        
</apply>
      
</apply>
      
      
<apply id="P_C2_diff_eq"><eq />
        
<apply><diff />
          
<bvar><ci> time </ci></bvar>
          
<ci> P_C2 </ci>
        
</apply>
        
<apply><minus />
          
<apply><times />
            
<ci> k_c_plus </ci>
            
<ci> P_O1 </ci>
          
</apply>
          
<apply><times />
            
<ci> k_c_minus </ci>
            
<ci> P_C2 </ci>
          
</apply>
        
</apply>
      
</apply>
    
</math>
  
</component>
  
  
<component name="SERCA_pump">
    
<variable name="J_up" public_interface="out" units="micromolar_per_millisecond" />
    
    
<variable name="k_fb" initial_value="0.24" units="micromolar" />
    
<variable name="k_rb" initial_value="1.64" units="millimolar" />
    
<variable name="fb" initial_value="0.292" units="micromolar_per_second" />
    
<variable name="rb" initial_value="0.311" units="micromolar_per_second" />
    
<variable name="Vmax_f" units="micromolar_per_second" />
    
<variable name="Vmax_r" units="micromolar_per_second" />
    
<variable name="n_fb" initial_value="1.4" units="dimensionless" />
    
<variable name="n_rb" units="dimensionless" />
    
    
<variable name="time" public_interface="in" units="millisecond" />
    
<variable name="Ca_NSR" public_interface="in" units="micromolar" />
    
<variable name="Cai" public_interface="in" units="micromolar" />
    
    
<math xmlns="http://www.w3.org/1998/Math/MathML">
      
<apply id="J_up_calculation"><eq />
        
<ci> J_up </ci>
        
<apply><divide />
          
<apply><minus />
            
<apply><times />
              
<ci> Vmax_f </ci>
              
<ci> fb </ci>
            
</apply>
            
<apply><times />
              
<ci> Vmax_r </ci>
              
<ci> rb </ci>
            
</apply>
          
</apply>
          
<apply><plus />
            
<cn cellml:units="dimensionless"> 1.0 </cn>
            
<ci> fb </ci>
            
<ci> rb </ci>
          
</apply>
        
</apply>
      
</apply>
      
      
<apply id="fb_calculation"><eq />
        
<ci> fb </ci>
        
<apply><power />
          
<apply><divide />
            
<ci> Cai </ci>
            
<ci> k_fb </ci>
          
</apply> 
          
<ci> n_fb </ci>
        
</apply> 
      
</apply> 
      
      
<apply id="rb_calculation"><eq />
        
<ci> rb </ci>
        
<apply><power />
          
<apply><divide />
            
<ci> Ca_NSR </ci>
            
<ci> k_rb </ci>
          
</apply> 
          
<ci> n_rb </ci>
        
</apply> 
      
</apply> 
    
</math>
  
</component>
  
  
<component name="intracellular_Ca_fluxes">
    
<variable name="J_rel" public_interface="out" units="micromolar_per_millisecond" />
    
<variable name="J_trpn" public_interface="out" units="micromolar_per_millisecond" />
    
<variable name="J_tr" public_interface="out" units="micromolar_per_millisecond" /> 
    
<variable name="J_xfer" public_interface="out" units="micromolar_per_millisecond" />
    
    
<variable name="v1" initial_value="3.6" units="per_millisecond" />
    
<variable name="tau_tr" initial_value="0.5747" units="millisecond" />
    
<variable name="tau_xfer" initial_value="9.09" units="millisecond" />
    
    
<variable name="HTRPN_tot" public_interface="in" units="micromolar" />
    
<variable name="LTRPN_tot" public_interface="in" units="micromolar" />
    
<variable name="HTRPNCa" public_interface="in" units="millimolar" />
    
<variable name="LTRPNCa" public_interface="in" units="millimolar" />
    
<variable name="k_htrpn_plus" public_interface="in" units="per_micromolar_per_second" />
    
<variable name="k_htrpn_minus" public_interface="in" units="per_second" />
    
<variable name="k_ltrpn_plus" public_interface="in" units="per_micromolar_per_second" />
    
<variable name="k_ltrpn_minus" public_interface="in" units="per_micromolar_per_second" />
    
<variable name="time" public_interface="in" units="millisecond" />
    
<variable name="P_O1" public_interface="in" units="dimensionless" />
    
<variable name="P_O2" public_interface="in" units="dimensionless" />
    
<variable name="Cai" public_interface="in" units="micromolar" />
    
<variable name="Ca_SS" public_interface="in" units="millimolar" />
    
<variable name="Ca_NSR" public_interface="in" units="micromolar" />
    
<variable name="Ca_JSR" public_interface="in" units="millimolar" />
    
    
<math xmlns="http://www.w3.org/1998/Math/MathML">
      
<apply id="J_rel_calculation"><eq />
        
<ci> J_rel </ci>
        
<apply><times />
          
<ci> v1 </ci>
          
<apply><plus />
            
<ci> P_O1 </ci>
            
<ci> P_O2 </ci>
          
</apply>
          
<apply><minus />
            
<ci> Ca_JSR </ci>
            
<ci> Ca_SS </ci>
          
</apply>
        
</apply>
      
</apply>
      
      
<apply id="J_tr_calculation"><eq />
        
<ci> J_tr </ci>
        
<apply><divide />
          
<apply><minus />
            
<ci> Ca_NSR </ci>
            
<ci> Ca_JSR </ci>
          
</apply>
          
<ci> tau_tr </ci>
        
</apply>
      
</apply>
      
      
<apply id="J_xfer_calculation"><eq />
        
<ci> J_xfer </ci>
        
<apply><divide />
          
<apply><minus />
            
<ci> Ca_SS </ci>
            
<ci> Cai </ci>
          
</apply>
          
<ci> tau_xfer </ci>
        
</apply>
      
</apply>
      
      
<apply id="J_trpn_calculation"><eq />
        
<ci> J_trpn </ci>
        
<apply><plus />
          
<apply><times />
            
<ci> k_htrpn_plus </ci>
            
<ci> Cai </ci>
            
<apply><minus />
              
<apply><minus />
                
<ci> HTRPN_tot </ci>
                
<ci> HTRPNCa </ci>
              
</apply>
              
<apply><times />
                
<ci> k_htrpn_minus </ci>
                
<ci> HTRPNCa </ci>
              
</apply>
            
</apply>
          
</apply>
          
<apply><times />
            
<ci> k_ltrpn_plus </ci>
            
<ci> Cai </ci>
            
<apply><minus />
              
<apply><minus />
                
<ci> LTRPN_tot </ci>
                
<ci> LTRPNCa </ci>
              
</apply>
              
<apply><times />
                
<ci> k_ltrpn_minus </ci>
                
<ci> LTRPNCa </ci>
              
</apply>
            
</apply>
          
</apply>
        
</apply>
      
</apply>
    
</math>
  
</component>
  
  
<component name="intracellular_ionic_concentrations">
    
<variable name="Nai" public_interface="out" units="millimolar" />
    
<variable
        
name="Nao" public_interface="out"
        
initial_value="140.0" units="millimolar" />
    
<variable name="Ki" public_interface="out" units="millimolar" />
    
<variable
        
name="Ko" public_interface="out"
        
initial_value="5.4" units="millimolar" />
    
<variable name="Cai" public_interface="out" units="millimolar" />
    
<variable
        
name="Cao" public_interface="out"
        
initial_value="1.8" units="millimolar" />
    
<variable name="Ca_SS" public_interface="out" units="millimolar" />
    
<variable name="Ca_NSR" public_interface="out" units="millimolar" />
    
<variable name="Ca_JSR" public_interface="out" units="millimolar" />
              
    
<variable name="betai" units="dimensionless" />
    
<variable name="beta_SS" units="dimensionless" />
    
<variable name="beta_JSR" units="dimensionless" />
    
<variable name="K_mCMDN" initial_value="2.38" units="micromolar" />
    
<variable name="K_mCSQN" initial_value="0.8" units="millimolar" />
    
<variable name="CSQN_tot" initial_value="15.0" units="millimolar" />
    
<variable name="CMDN_tot" initial_value="50.0" units="micromolar" />
              
    
<variable name="time" public_interface="in" units="millisecond" />
    
<variable name="J_rel" public_interface="in" units="micromolar_per_millisecond" />
    
<variable name="J_up" public_interface="in" units="micromolar_per_millisecond" />
    
<variable name="J_tr" public_interface="in" units="micromolar_per_millisecond" />
    
<variable name="J_xfer" public_interface="in" units="micromolar_per_millisecond" />
    
<variable name="J_trpn" public_interface="in" units="micromolar_per_millisecond" />
    
<variable name="F" public_interface="in" units="coulomb_per_millimole" />
    
<variable name="i_Na" public_interface="in" units="microA_per_microF" />
    
<variable name="i_Na_b" public_interface="in" units="microA_per_microF" />
    
<variable name="i_ns_Na" public_interface="in" units="microA_per_microF" />
    
<variable name="i_NaCa" public_interface="in" units="microA_per_microF" />
    
<variable name="i_NaK" public_interface="in" units="microA_per_microF" />
    
<variable name="i_Ca" public_interface="in" units="microA_per_microF" />
    
<variable name="i_p_Ca" public_interface="