- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2009-06-17 15:20:34+12:00
- Desc:
- committing version04 of noble_noble_bett_earm_ho_so_1991
- Permanent Source URI:
- http://models.cellml.org/workspace/noble_noble_bett_earm_ho_so_1991/rawfile/3844781835a4a3e214fa6b54b607e975905f9ecd/noble_noble_bett_earm_ho_so_1991.cellml
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This CellML file was generated on 26/09/2007 at 15:17:37 using:
COR (0.9.31.789)
Copyright 2002-2007 Dr Alan Garny
http://COR.physiol.ox.ac.uk/ - COR@physiol.ox.ac.uk
CellML 1.0 was used to generate this cellular model
http://www.CellML.org/
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<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<section id="sec_status">
<title>Model Status</title>
<para>
This model has been curated and unit-checked by Penny Noble of Oxford University and supports simulation of multiple action potentials. This model is known to run in COR and PCEnv and also has a PCEnv session file associated with it.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Introduction: The idea that sodium-calcium exchange might generate a current during cardiac electrical activity was first raised as a possible mechanism for the pathological situation when calcium-overloaded tissue generates the transient inward current responsible for ectopic beating. This was one of the mechanisms proposed by Kass, Lederer, Tsien,
and Weingart in 1978. Mullins had already suggested on theoretical grounds that a variety of currents flowing across the cardiac cell membrane might be carried by sodium-calcium exchange. With regard to the transient inward current, the evidence that it is carried mostly (though not entirely) by sodium-calcium exchange is now very strong in ventricular cells,4 and it has proved possible to reproduce this mechanism in computer models of cardiac electrical activity. The purpose of the present paper is to review the evidence, experimental and theoretical, for a major role
of the sodium-calcium exchange current during normal cardiac rhythm.
</para>
<para>
Brown et al. and Arlock and Noble recorded slow components of inward current following the calcium current that were attributed to sodium-calcium exchange activated by the intracellular calcium transient, while Mitchell et al. and Schouten and ter Keurs showed that the exchange current could play a major role in maintaining the late low plateau in rat ventricular cells. Several years previously Simurda et al. showed that a component of inward current during weak depolarizations is directly proportional to contractile force, suggesting that it was calcium activated.
</para>
<para>
Until 1987 it has to be admitted that these explanations were always subject to the criticism that the currents concerned were measured in highly complex situations with many other current components also present. Of course, if the role of sodium-calcium exchange during normal cellular activity is to be assessed, such experiments are necessary,
and we will describe more of them later in this paper. But they need to be backed up by experiments done under conditions where the exchange current is isolated from other components. This was first achieved by Kimura, Miyamae, and Noma in 1987. The results were very relevant indeed, not only because they showed the electrogenic
nature of the sodium-calcium exchange in cardiac cells (including demonstrating that
its most likely stoichiometry was 3 : 1) but also because the current-voltage relations
obtained were very similar to those required theoretically in modeling work to explain the results obtained in normal beating cardiac tissue.
</para>
<para>
It is no longer necessary, therefore, to prove the hypothesis that sodium-calcium exchange contributes a significant electric current. The question now is rather a functional one: How large can this current be and can it be sufficient to be primarily responsible for maintaining calcium balance in the heart by generating the major
component of calcium efflux? This is the hypothesis that led to the experimental and
modeling work done by Hilgemann and Noble. In this paper, we will describe experiments done on atrial and ventricular cells that attempt to refine this hypothesis. We will raise the question of how the contribution of
sodium-calcium exchange to the action potential varies with the region of the heart from which the cells come, with the ionic concentration levels (in particular of internal ion concentrations) and with inotropic state.
</para>
<para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="noble_1991.png"/>
</imageobject>
</mediaobject>
<caption>A schematic diagram describing the current flows across the cell membrane that are captured in the Noble 1991 model.</caption>
</informalfigure>
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://www3.interscience.wiley.com/journal/119349583/abstract">The Role of Sodium-Calcium Exchange During the Cardiac Action Potential</ulink>, by Noble D, Noble SJ, Bett GC, Earm YE, Ho WK, So IK, Annals of the New York Academy of Sciences 1991;639:334-53.
</para>
<para>
A <ulink url="http://www3.interscience.wiley.com/cgi-bin/fulltext/119349583/PDFSTART">PDF version</ulink> of the article is also available.
</para>
<para>
<ulink url="http://www.ncbi.nlm.nih.gov/pubmed/1785860">PubMed ID: 1785860 </ulink>
</para>
<para>
</para>
</sect1>
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</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>beta_m</ci>
<apply>
<times/>
<cn cellml:units="per_second">8000</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_millivolt">0.056</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">66</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<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</cn>
<ci>m</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_m</ci>
<ci>m</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="fast_sodium_current_h_gate">
<variable units="dimensionless" public_interface="out" name="h" initial_value="0.99816539"/>
<variable units="per_second" name="alpha_h"/>
<variable units="per_second" name="beta_h"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>alpha_h</ci>
<apply>
<times/>
<cn cellml:units="per_second">20</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_millivolt">0.125</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">75</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_h</ci>
<apply>
<divide/>
<cn cellml:units="per_second">2000</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<times/>
<cn cellml:units="dimensionless">320</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_millivolt">0.1</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">75</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<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</cn>
<ci>h</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_h</ci>
<ci>h</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sodium_background_current">
<variable units="nanoA" public_interface="out" name="i_b_Na"/>
<variable units="microS" name="g_bna" initial_value="0.0006"/>
<variable units="millimolar" public_interface="in" name="Na_i"/>
<variable units="millivolt" public_interface="in" name="E_Na"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_b_Na</ci>
<apply>
<times/>
<ci>g_bna</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Na</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel">
<variable units="nanoA" public_interface="out" name="i_Ca_L_Ca"/>
<variable units="nanoA" public_interface="out" name="i_Ca_L_K"/>
<variable units="nanoA" public_interface="out" name="i_Ca_L_Na"/>
<variable units="nanoA" public_interface="out" name="i_Ca_L"/>
<variable units="nanoA_per_millimolar" name="P_Ca_L" initial_value="0.25"/>
<variable units="dimensionless" name="P_CaK" initial_value="0.002"/>
<variable units="dimensionless" name="P_CaNa" initial_value="0.01"/>
<variable units="millimolar" public_interface="in" name="Ca_o"/>
<variable units="millimolar" public_interface="in" private_interface="out" name="Ca_i"/>
<variable units="millimolar" public_interface="in" name="K_o"/>
<variable units="millimolar" public_interface="in" name="K_i"/>
<variable units="millimolar" public_interface="in" name="Na_o"/>
<variable units="millimolar" public_interface="in" name="Na_i"/>
<variable units="joule_per_kilomole_kelvin" public_interface="in" name="R"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="second" public_interface="in" private_interface="out" name="time"/>
<variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
<variable units="dimensionless" private_interface="in" name="d"/>
<variable units="dimensionless" private_interface="in" name="f"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_Ca_L_Ca</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">4</cn>
<ci>P_Ca_L</ci>
<ci>d</ci>
<ci>f</ci>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
<ci>F</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>Ca_i</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="millivolt">100</cn>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>Ca_o</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
<ci>F</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_Ca_L_K</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<divide/>
<apply>
<times/>
<ci>P_CaK</ci>
<ci>P_Ca_L</ci>
<ci>d</ci>
<ci>f</ci>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>K_i</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="millivolt">50</cn>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>K_o</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_Ca_L_Na</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<divide/>
<apply>
<times/>
<ci>P_CaNa</ci>
<ci>P_Ca_L</ci>
<ci>d</ci>
<ci>f</ci>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>Na_i</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="millivolt">50</cn>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>Na_o</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_Ca_L</ci>
<apply>
<plus/>
<ci>i_Ca_L_Ca</ci>
<ci>i_Ca_L_K</ci>
<ci>i_Ca_L_Na</ci>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel_d_gate">
<variable units="dimensionless" public_interface="out" name="d" initial_value="0"/>
<variable units="per_second" name="alpha_d"/>
<variable units="per_second" name="beta_d"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="millivolt" name="E0_d"/>
<variable units="dimensionless" name="speed_d" initial_value="3"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>E0_d</ci>
<apply>
<minus/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">24</cn>
</apply>
<cn cellml:units="millivolt">5</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>alpha_d</ci>
<piecewise>
<piece>
<cn cellml:units="per_second">120</cn>
<apply>
<lt/>
<apply>
<abs/>
<ci>E0_d</ci>
</apply>
<cn cellml:units="millivolt">0.0001</cn>
</apply>
</piece>
<otherwise>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_millivolt_second">30</cn>
<ci>E0_d</ci>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>E0_d</ci>
</apply>
<cn cellml:units="millivolt">4</cn>
</apply>
</apply>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>beta_d</ci>
<piecewise>
<piece>
<cn cellml:units="per_second">120</cn>
<apply>
<lt/>
<apply>
<abs/>
<ci>E0_d</ci>
</apply>
<cn cellml:units="millivolt">0.0001</cn>
</apply>
</piece>
<otherwise>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_millivolt_second">12</cn>
<ci>E0_d</ci>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<ci>E0_d</ci>
<cn cellml:units="millivolt">10</cn>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>d</ci>
</apply>
<apply>
<times/>
<ci>speed_d</ci>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_d</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>d</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_d</ci>
<ci>d</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel_f_gate">
<variable units="dimensionless" public_interface="out" name="f" initial_value="1"/>
<variable units="per_second" name="alpha_f"/>
<variable units="per_second" name="beta_f"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="dimensionless" name="speed_f" initial_value="0.5"/>
<variable units="millivolt" name="delta_f" initial_value="0.0001"/>
<variable units="millivolt" name="E0_f"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>E0_f</ci>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">34</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>alpha_f</ci>
<piecewise>
<piece>
<cn cellml:units="per_second">25</cn>
<apply>
<lt/>
<apply>
<abs/>
<ci>E0_f</ci>
</apply>
<ci>delta_f</ci>
</apply>
</piece>
<otherwise>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_millivolt_second">6.25</cn>
<ci>E0_f</ci>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<ci>E0_f</ci>
<cn cellml:units="millivolt">4</cn>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>beta_f</ci>
<apply>
<divide/>
<cn cellml:units="per_second">50</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">34</cn>
</apply>
</apply>
<cn cellml:units="millivolt">4</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>f</ci>
</apply>
<apply>
<times/>
<ci>speed_f</ci>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_f</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>f</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_f</ci>
<ci>f</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="calcium_background_current">
<variable units="nanoA" public_interface="out" name="i_b_Ca"/>
<variable units="microS" name="g_bca" initial_value="0.00025"/>
<variable units="millivolt" public_interface="in" name="E_Ca"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_b_Ca</ci>
<apply>
<times/>
<ci>g_bca</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Ca</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="transient_outward_current">
<variable units="nanoA" public_interface="out" name="i_to"/>
<variable units="microS" name="g_to" initial_value="0.005"/>
<variable units="dimensionless" name="g_tos" initial_value="0"/>
<variable units="millivolt" public_interface="in" name="E_K"/>
<variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
<variable units="second" public_interface="in" private_interface="out" name="time"/>
<variable units="dimensionless" private_interface="in" name="s"/>
<variable units="dimensionless" private_interface="in" name="r"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_to</ci>
<apply>
<times/>
<ci>g_to</ci>
<apply>
<plus/>
<ci>g_tos</ci>
<apply>
<times/>
<ci>s</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>g_tos</ci>
</apply>
</apply>
</apply>
<ci>r</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="transient_outward_current_s_gate">
<variable units="dimensionless" public_interface="out" name="s" initial_value="1"/>
<variable units="per_second" name="alpha_s"/>
<variable units="per_second" name="beta_s"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>alpha_s</ci>
<apply>
<times/>
<cn cellml:units="per_second">0.033</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>V</ci>
</apply>
<cn cellml:units="millivolt">17</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_s</ci>
<apply>
<divide/>
<cn cellml:units="per_second">33</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_millivolt">0.125</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">10</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>s</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_s</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>s</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_s</ci>
<ci>s</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="transient_outward_current_r_gate">
<variable units="dimensionless" public_interface="out" name="r" initial_value="0"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>r</ci>
</apply>
<apply>
<times/>
<cn cellml:units="per_second">333</cn>
<apply>
<minus/>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">4</cn>
</apply>
</apply>
<cn cellml:units="millivolt">5</cn>
</apply>
</apply>
</apply>
</apply>
<ci>r</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sodium_potassium_pump">
<variable units="nanoA" public_interface="out" name="i_NaK"/>
<variable units="nanoA" name="i_NaK_max" initial_value="0.7"/>
<variable units="millimolar" name="K_mK" initial_value="1"/>
<variable units="millimolar" name="K_mNa" initial_value="40"/>
<variable units="millimolar" public_interface="in" name="K_o"/>
<variable units="millimolar" public_interface="in" name="Na_i"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_NaK</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>i_NaK_max</ci>
<ci>K_o</ci>
</apply>
<apply>
<plus/>
<ci>K_mK</ci>
<ci>K_o</ci>
</apply>
</apply>
<ci>Na_i</ci>
</apply>
<apply>
<plus/>
<ci>K_mNa</ci>
<ci>Na_i</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sodium_calcium_exchanger">
<variable units="nanoA" public_interface="out" name="i_NaCa"/>
<variable units="nanoA" name="k_NaCa" initial_value="0.0005"/>
<variable units="dimensionless" name="n_NaCa" initial_value="3"/>
<variable units="dimensionless" name="d_NaCa" initial_value="0"/>
<variable units="dimensionless" name="gamma" initial_value="0.5"/>
<variable units="millimolar" public_interface="in" name="Na_i"/>
<variable units="millimolar" public_interface="in" name="Na_o"/>
<variable units="millimolar" public_interface="in" name="Ca_i"/>
<variable units="millimolar" public_interface="in" name="Ca_o"/>
<variable units="joule_per_kilomole_kelvin" public_interface="in" name="R"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_NaCa</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>k_NaCa</ci>
<apply>
<minus/>
<apply>
<times/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci>gamma</ci>
<apply>
<minus/>
<ci>n_NaCa</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<power/>
<ci>Na_i</ci>
<ci>n_NaCa</ci>
</apply>
<ci>Ca_o</ci>
</apply>
<apply>
<times/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>gamma</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<minus/>
<ci>n_NaCa</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<power/>
<ci>Na_o</ci>
<ci>n_NaCa</ci>
</apply>
<ci>Ca_i</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="millimolar4">1</cn>
<apply>
<times/>
<ci>d_NaCa</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>Ca_i</ci>
<apply>
<power/>
<ci>Na_o</ci>
<ci>n_NaCa</ci>
</apply>
</apply>
<apply>
<times/>
<ci>Ca_o</ci>
<apply>
<power/>
<ci>Na_i</ci>
<ci>n_NaCa</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>Ca_i</ci>
<cn cellml:units="millimolar">0.0069</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sarcoplasmic_reticulum_calcium_pump">
<variable units="millimolar_per_second" public_interface="out" name="i_up"/>
<variable units="dimensionless" name="K_1"/>
<variable units="millimolar" name="K_2"/>
<variable units="millimolar" name="K_cyca" initial_value="0.0003"/>
<variable units="dimensionless" name="K_xcs" initial_value="0.4"/>
<variable units="millimolar" name="K_srca" initial_value="0.5"/>
<variable units="millimolar_per_second" name="alpha_up" initial_value="0.4"/>
<variable units="millimolar_per_second" name="beta_up" initial_value="0.03"/>
<variable units="millimolar" public_interface="in" name="Ca_i"/>
<variable units="millimolar" public_interface="in" name="Ca_up"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>K_1</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>K_cyca</ci>
<ci>K_xcs</ci>
</apply>
<ci>K_srca</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>K_2</ci>
<apply>
<plus/>
<ci>Ca_i</ci>
<apply>
<times/>
<ci>Ca_up</ci>
<ci>K_1</ci>
</apply>
<apply>
<times/>
<ci>K_cyca</ci>
<ci>K_xcs</ci>
</apply>
<ci>K_cyca</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>i_up</ci>
<apply>
<minus/>
<apply>
<times/>
<apply>
<divide/>
<ci>Ca_i</ci>
<ci>K_2</ci>
</apply>
<ci>alpha_up</ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>Ca_up</ci>
<ci>K_1</ci>
</apply>
<ci>K_2</ci>
</apply>
<ci>beta_up</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="calcium_translocation">
<variable units="millimolar_per_second" public_interface="out" name="i_trans"/>
<variable units="millimolar" public_interface="in" name="Ca_rel"/>
<variable units="millimolar" public_interface="in" name="Ca_up"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_trans</ci>
<apply>
<times/>
<cn cellml:units="per_second">50</cn>
<apply>
<minus/>
<ci>Ca_up</ci>
<ci>Ca_rel</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="calcium_release">
<variable units="millimolar_per_second" public_interface="out" name="i_rel"/>
<variable units="dimensionless" name="VoltDep"/>
<variable units="dimensionless" name="RegBindSite"/>
<variable units="per_second" name="ActRate"/>
<variable units="per_second" name="InactRate"/>
<variable units="per_second" name="K_leak_rate" initial_value="0"/>
<variable units="per_second" name="K_m_rel" initial_value="250"/>
<variable units="dimensionless" name="PrecFrac"/>
<variable units="dimensionless" name="ActFrac" initial_value="0"/>
<variable units="dimensionless" name="ProdFrac" initial_value="0"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="millimolar" public_interface="in" name="Ca_i"/>
<variable units="millimolar" public_interface="in" name="Ca_rel"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>VoltDep</ci>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="per_millivolt">0.08</cn>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">40</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>RegBindSite</ci>
<apply>
<power/>
<apply>
<divide/>
<ci>Ca_i</ci>
<apply>
<plus/>
<ci>Ca_i</ci>
<cn cellml:units="millimolar">0.0005</cn>
</apply>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>ActRate</ci>
<apply>
<times/>
<cn cellml:units="per_second">500</cn>
<ci>RegBindSite</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>InactRate</ci>
<apply>
<plus/>
<cn cellml:units="per_second">60</cn>
<apply>
<times/>
<cn cellml:units="per_second">500</cn>
<ci>RegBindSite</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>PrecFrac</ci>
<apply>
<minus/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>ActFrac</ci>
</apply>
<ci>ProdFrac</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ActFrac</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>PrecFrac</ci>
<ci>ActRate</ci>
</apply>
<apply>
<times/>
<ci>ActFrac</ci>
<ci>InactRate</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ProdFrac</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>ActFrac</ci>
<ci>InactRate</ci>
</apply>
<apply>
<times/>
<cn cellml:units="per_second">1</cn>
<ci>ProdFrac</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_rel</ci>
<apply>
<times/>
<apply>
<plus/>
<apply>
<times/>
<apply>
<power/>
<apply>
<divide/>
<ci>ActFrac</ci>
<apply>
<plus/>
<ci>ActFrac</ci>
<cn cellml:units="dimensionless">0.25</cn>
</apply>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>K_m_rel</ci>
</apply>
<ci>K_leak_rate</ci>
</apply>
<ci>Ca_rel</ci>
</apply>
</apply>
</math>
</component>
<component name="extracellular_sodium_concentration">
<variable units="millimolar" public_interface="out" name="Na_o" initial_value="140"/>
</component>
<component name="intracellular_sodium_concentration">
<variable units="millimolar" public_interface="out" name="Na_i" initial_value="5"/>
<variable units="micrometre3" public_interface="in" name="V_i"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="nanoA" public_interface="in" name="i_Na"/>
<variable units="nanoA" public_interface="in" name="i_b_Na"/>
<variable units="nanoA" public_interface="in" name="i_Ca_L_Na"/>
<variable units="nanoA" public_interface="in" name="i_NaK"/>
<variable units="nanoA" public_interface="in" name="i_NaCa"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Na_i</ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<apply>
<minus/>
<cn cellml:units="mA_nA">1</cn>
</apply>
<apply>
<times/>
<cn cellml:units="litre_micrometre3">1</cn>
<ci>V_i</ci>
<ci>F</ci>
</apply>
</apply>
<apply>
<plus/>
<ci>i_Na</ci>
<ci>i_b_Na</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">3</cn>
<ci>i_NaK</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">3</cn>
<ci>i_NaCa</ci>
</apply>
<ci>i_Ca_L_Na</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="extracellular_calcium_concentration">
<variable units="millimolar" public_interface="out" name="Ca_o" initial_value="2"/>
</component>
<component name="extracellular_potassium_concentration">
<variable units="millimolar" public_interface="out" name="K_o" initial_value="4"/>
</component>
<component name="intracellular_potassium_concentration">
<variable units="millimolar" public_interface="out" name="K_i" initial_value="140"/>
<variable units="micrometre3" public_interface="in" name="V_i"/>
<variable units="nanoA" public_interface="in" name="i_K1"/>
<variable units="nanoA" public_interface="in" name="i_K"/>
<variable units="nanoA" public_interface="in" name="i_Ca_L_K"/>
<variable units="nanoA" public_interface="in" name="i_to"/>
<variable units="nanoA" public_interface="in" name="i_b_K"/>
<variable units="nanoA" public_interface="in" name="i_NaK"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>K_i</ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<apply>
<minus/>
<cn cellml:units="mA_nA">1</cn>
</apply>
<apply>
<times/>
<cn cellml:units="litre_micrometre3">1</cn>
<ci>V_i</ci>
<ci>F</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>i_K1</ci>
<ci>i_K</ci>
<ci>i_Ca_L_K</ci>
<ci>i_to</ci>
<ci>i_b_K</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>i_NaK</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="intracellular_calcium_concentration">
<variable units="millimolar" public_interface="out" name="Ca_i" initial_value="7.63e-6"/>
<variable units="millimolar" public_interface="out" name="Ca_up" initial_value="0.3013"/>
<variable units="millimolar" public_interface="out" name="Ca_rel" initial_value="0.2989"/>
<variable units="millimolar" name="Ca_Calmod" initial_value="0.0003"/>
<variable units="millimolar" name="Ca_Trop" initial_value="0.0002"/>
<variable units="millimolar" name="Calmod" initial_value="0.02"/>
<variable units="millimolar" name="Trop" initial_value="0.05"/>
<variable units="per_millimolar_second" name="alpha_Calmod" initial_value="100000"/>
<variable units="per_second" name="beta_Calmod" initial_value="50"/>
<variable units="per_millimolar_second" name="alpha_Trop" initial_value="100000"/>
<variable units="per_second" name="beta_Trop" initial_value="200"/>
<variable units="micrometre" name="radius" initial_value="0.012"/>
<variable units="micrometre" name="length" initial_value="0.074"/>
<variable units="micrometre3" public_interface="out" name="V_i"/>
<variable units="micrometre3" name="V_Cell"/>
<variable units="dimensionless" name="V_i_ratio"/>
<variable units="dimensionless" name="V_rel_ratio" initial_value="0.1"/>
<variable units="dimensionless" name="V_e_ratio" initial_value="0.4"/>
<variable units="dimensionless" name="V_up_ratio" initial_value="0.01"/>
<variable units="millimolar_per_second" public_interface="in" name="i_up"/>
<variable units="millimolar_per_second" public_interface="in" name="i_trans"/>
<variable units="millimolar_per_second" public_interface="in" name="i_rel"/>
<variable units="nanoA" public_interface="in" name="i_NaCa"/>
<variable units="nanoA" public_interface="in" name="i_Ca_L_Ca"/>
<variable units="nanoA" public_interface="in" name="i_b_Ca"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_Cell</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">3.141592654</cn>
<apply>
<power/>
<ci>radius</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>length</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>V_i_ratio</ci>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>V_e_ratio</ci>
</apply>
<ci>V_up_ratio</ci>
</apply>
<ci>V_rel_ratio</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>V_i</ci>
<apply>
<times/>
<ci>V_Cell</ci>
<ci>V_i_ratio</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_i</ci>
</apply>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<minus/>
<cn cellml:units="mA_nA">1</cn>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<cn cellml:units="litre_micrometre3">1</cn>
<ci>V_i</ci>
<ci>F</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>i_Ca_L_Ca</ci>
<ci>i_b_Ca</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>i_NaCa</ci>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>i_rel</ci>
<ci>V_rel_ratio</ci>
</apply>
<ci>V_i_ratio</ci>
</apply>
</apply>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_Calmod</ci>
</apply>
</apply>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_Trop</ci>
</apply>
</apply>
<ci>i_up</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_up</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<apply>
<divide/>
<ci>V_i_ratio</ci>
<ci>V_up_ratio</ci>
</apply>
<ci>i_up</ci>
</apply>
<ci>i_trans</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_rel</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<apply>
<divide/>
<ci>V_up_ratio</ci>
<ci>V_rel_ratio</ci>
</apply>
<ci>i_trans</ci>
</apply>
<ci>i_rel</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_Calmod</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_Calmod</ci>
<ci>Ca_i</ci>
<apply>
<minus/>
<ci>Calmod</ci>
<ci>Ca_Calmod</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_Calmod</ci>
<ci>Ca_Calmod</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_Trop</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_Trop</ci>
<ci>Ca_i</ci>
<apply>
<minus/>
<ci>Trop</ci>
<ci>Ca_Trop</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_Trop</ci>
<ci>Ca_Trop</ci>
</apply>
</apply>
</apply>
</math>
</component>
<group>
<relationship_ref relationship="containment"/>
<component_ref component="membrane">
<component_ref component="fast_sodium_current">
<component_ref component="fast_sodium_current_m_gate"/>
<component_ref component="fast_sodium_current_h_gate"/>
</component_ref>
<component_ref component="L_type_Ca_channel">
<component_ref component="L_type_Ca_channel_d_gate"/>
<component_ref component="L_type_Ca_channel_f_gate"/>
</component_ref>
<component_ref component="time_dependent_potassium_current">
<component_ref component="time_dependent_potassium_current_x_gate"/>
</component_ref>
<component_ref component="potassium_background_current"/>
<component_ref component="time_independent_potassium_current"/>
<component_ref component="sodium_background_current"/>
<component_ref component="calcium_background_current"/>
<component_ref component="transient_outward_current">
<component_ref component="transient_outward_current_s_gate"/>
<component_ref component="transient_outward_current_r_gate"/>
</component_ref>
<component_ref component="sodium_potassium_pump"/>
<component_ref component="sodium_calcium_exchanger"/>
<component_ref component="sarcoplasmic_reticulum_calcium_pump"/>
<component_ref component="calcium_translocation"/>
<component_ref component="calcium_release"/>
<component_ref component="extracellular_sodium_concentration"/>
<component_ref component="intracellular_sodium_concentration"/>
<component_ref component="extracellular_potassium_concentration"/>
<component_ref component="intracellular_potassium_concentration"/>
<component_ref component="extracellular_calcium_concentration"/>
<component_ref component="intracellular_calcium_concentration"/>
<component_ref component="reversal_potentials"/>
</component_ref>
</group>
<group>
<relationship_ref relationship="encapsulation"/>
<component_ref component="fast_sodium_current">
<component_ref component="fast_sodium_current_m_gate"/>
<component_ref component="fast_sodium_current_h_gate"/>
</component_ref>
<component_ref component="L_type_Ca_channel">
<component_ref component="L_type_Ca_channel_d_gate"/>
<component_ref component="L_type_Ca_channel_f_gate"/>
</component_ref>
<component_ref component="transient_outward_current">
<component_ref component="transient_outward_current_s_gate"/>
<component_ref component="transient_outward_current_r_gate"/>
</component_ref>
<component_ref component="time_dependent_potassium_current">
<component_ref component="time_dependent_potassium_current_x_gate"/>
</component_ref>
</group>
<connection>
<map_components component_2="environment" component_1="membrane"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="reversal_potentials"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="fast_sodium_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
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<rdf:value>Version 03 was created by Penny Noble of Oxford University and supports simulation of multiple action potentials. This model is known to run in COR and PCEnv. This model also has a PCEnv session file associated with it.</rdf:value>
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<vCard:Given>Penny</vCard:Given>
<vCard:Family>Noble</vCard:Family>
<vCard:Other>J</vCard:Other>
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<vCard:Given>G</vCard:Given>
<vCard:Family>Bett</vCard:Family>
<vCard:Other>C</vCard:Other>
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<rdf:value>penny.noble@dpag.ox.ac.uk</rdf:value>
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<rdf:Description rdf:about="rdf:#14b9e56f-e644-4ef9-8c50-791b4a3811be">
<dcterms:W3CDTF>2007-01-16T00:00:00+00:00</dcterms:W3CDTF>
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<rdf:Description rdf:about="rdf:#907d074c-ea4e-46f7-bb65-934a3d292b16">
<dc:title>Annals of the New York Academy of Sciences</dc:title>
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<rdf:value>Units checked, curated.</rdf:value>
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<ns7:nonstandard-pointDensity>100000</ns7:nonstandard-pointDensity>
<ns7:maximumStepSize>0.001</ns7:maximumStepSize>
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<rdf:Description rdf:about="rdf:#b3a90496-864d-481e-9d4d-080ff4c41dd6">
<dcterms:W3CDTF>2007-01-18T13:25:00+13:00</dcterms:W3CDTF>
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<dcterms:modified rdf:resource="rdf:#b9020ad6-31dc-41b5-86f7-bfe831fd76ef"/>
<rdf:value>Several variables were given cmeta:id's to allow creation of a PCEnv session.</rdf:value>
<cmeta:modifier rdf:resource="rdf:#c0c3e76f-2979-4b40-8e7c-764b1992cd49"/>
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<dcterms:W3CDTF>2007-04-22T13:25:00+12:00</dcterms:W3CDTF>
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<dc:creator rdf:resource="rdf:#d8c51369-3877-459c-a305-f9d372959f96"/>
<dc:title>The Role of Sodium-Calcium Exchange During the Cardiac Action Potential</dc:title>
<bqs:volume>639</bqs:volume>
<bqs:first_page>344</bqs:first_page>
<bqs:Journal rdf:resource="rdf:#907d074c-ea4e-46f7-bb65-934a3d292b16"/>
<dcterms:issued rdf:resource="rdf:#93b01751-5be2-493b-b4e6-487c8d62a683"/>
<bqs:last_page>353</bqs:last_page>
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<rdf:Description rdf:about="rdf:#0d1eeed2-444b-4102-a157-ca45dbd1b666">
<dcterms:W3CDTF>2007-11-29T12:49:02+13:00</dcterms:W3CDTF>
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<rdf:Description rdf:about="rdf:#f25e7b80-46e8-4a74-9c36-14c794781bdf">
<vCard:ORG rdf:resource="rdf:#db578964-9744-42e2-a1cb-502d07552ea0"/>
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<dcterms:modified rdf:resource="rdf:#b3a90496-864d-481e-9d4d-080ff4c41dd6"/>
<rdf:value>This model was curated by Penny Noble of Oxford University</rdf:value>
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<vCard:Given>Penny</vCard:Given>
<vCard:Family>Noble</vCard:Family>
<vCard:Other>J</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#59f441e3-4438-4a51-b1b5-c1cd9068ef9d">
<vCard:Given>Y</vCard:Given>
<vCard:Family>Earm</vCard:Family>
<vCard:Other>E</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#7f1d0e6e-9b50-4221-b575-04c9180e3b10">
<dcterms:W3CDTF>2006-01-01</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#db578964-9744-42e2-a1cb-502d07552ea0">
<vCard:Orgname>Oxford University</vCard:Orgname>
<vCard:Orgunit>Department of Physiology, Anatomy & Genetics</vCard:Orgunit>
</rdf:Description>
<rdf:Description rdf:about="rdf:#48b1321c-d699-4e06-a6d7-532a590dd44a">
<vCard:FN>James Lawson</vCard:FN>
</rdf:Description>
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<vCard:Given>James</vCard:Given>
<vCard:Family>Lawson</vCard:Family>
<vCard:Other>Richard</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#bf2fdf56-3e26-4b05-9633-335c161e8dc0">
<dcterms:modified rdf:resource="rdf:#015f3a32-5d5d-4c02-959d-5a1122d6bea7"/>
<rdf:value>A stimulus protocol component was added to the model using the amplitude (-6 nanoamps) and duration (1 ms) that was defined for the original single stimulus in the first version of the model. </rdf:value>
<cmeta:modifier rdf:resource="rdf:#f0a25543-60d1-4771-a06f-e4fb26b1ffb4"/>
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<rdf:Description rdf:about="rdf:#$AhV7g1">
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<rdf:Description rdf:about="rdf:#212f0d3f-daf1-4e52-9ee1-44cb7299e8de">
<vCard:Given>I</vCard:Given>
<vCard:Family>So</vCard:Family>
<vCard:Other>K</vCard:Other>
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<rdf:Description rdf:about="rdf:#663635ae-7df5-446b-9f76-e08bd96c4643">
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<rdf:value>This file contains a CellML 1.0 description of Noble, Noble, Bett, Earm, Ho and So's 1991 computational model of the cardiac action potential, emphasising the effect of the sodium-calcium exchanger on the AP.</rdf:value>
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<vCard:Given>D</vCard:Given>
<vCard:Family>Noble</vCard:Family>
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</model>
