- Author:
- Hanne <Hanne@hanne-nielsens-macbook.local>
- Date:
- 2010-05-11 12:25:02+12:00
- Desc:
- Integrated SVG image, added xul from 1994 model
- Permanent Source URI:
- https://models.cellml.org/workspace/demir_clark_giles_1999/rawfile/9bab6a6cf97e2b5f4ff8126958ed391e85d59728/demir_clark_giles_1999.cellml
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<!--
This CellML file was generated on 27/02/2007 at 15:14:55 using:
COR (0.9.31.457)
Copyright 2002-2006 Oxford Cardiac Electrophysiology Group
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/
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xml:base="" cmeta:id="demir_SAN_1999" name="demir_clark_giles_1999">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>A Model Of Parasympathetic Modulation Of Pacemaker Rate, 1999</title>
<author>
<firstname>Penny</firstname>
<surname>Noble</surname>
<affiliation>
<shortaffil>Oxford University</shortaffil>
</affiliation>
</author>
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<section id="sec_status">
<title>Model Status</title>
<para>
This model has been validated by Penny Noble of Oxford University and is known to run in COR and PCEnv to reproduce the published results. A PCEnv session file is also associated with this version. The units have been checked and are balanced.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: We have extended our compartmental model [Am. J. Physiol. 266 (Cell Physiol. 35): C832-C852, 1994] of the single rabbit sinoatrial node (SAN) cell so that it can simulate cellular responses to bath applications of ACh and isoprenaline as well as the effects of neuronally released ACh. The model employs three different types of muscarinic receptors to explain the variety of responses observed in mammalian cardiac pacemaking cells subjected to vagal stimulation. The response of greatest interest is the ACh-sensitive change in cycle length that is not accompanied by a change in action potential duration or repolarization or hyperpolarization of the maximum diastolic potential. In this case, an ACh-sensitive K+ current is not involved. Membrane hyperpolarization occurs in response to much higher levels of vagal stimulation, and this response is also mimicked by the model. Here, an ACh-sensitive K+ current is involved. The well-known phase-resetting response of the SAN cell to single and periodically applied vagal bursts of impulses is also simulated in the presence and absence of the beta-agonist isoprenaline. Finally, the responses of the SAN cell to longer continuous trains of periodic vagal stimulation are simulated, and this can result in the complete cessation of pacemaking. Therefore, this model is 1) applicable over the full range of intensity and pattern of vagal input and 2) can offer biophysically based explanations for many of the phenomena associated with the autonomic control of cardiac pacemaking.
</para>
<para>
The original paper reference is cited below:
</para>
<para>
Parasympathetic modulation of sinoatrial node pacemaker activity in rabbit heart: a unifying model, Semahat S. Demir, John W. Clark and Wayne R. Giles, 1999,
<emphasis>American Journal of Physiology</emphasis>, 276, H2221-H2244. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10362707&dopt=Abstract">PubMed ID: 10362707</ulink>
</para>
<informalfigure float="0" id="fig_cell_diagram">
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<imageobject>
<objectinfo>
<title>cell diagram of the Demir et al SAN model showing ionic currents, pumps and exchangers within the sarcolemma</title>
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<caption>A schematic diagram describing the current flows across the cell membrane that are captured in the Demir <emphasis>et al</emphasis> 1999 model of the electrophysiological activity in a SAN cell.</caption>
</informalfigure>
</sect1>
</article>
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<apply>
<minus/>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.208</cn>
</apply>
<ci>V</ci>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_d_L</ci>
<apply>
<divide/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt_second">11.43</cn>
<apply>
<minus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">5</cn>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.4</cn>
<apply>
<minus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">5</cn>
</apply>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_d_L</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<ci>alpha_d_L</ci>
<ci>beta_d_L</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>d_L_infinity</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">14.1</cn>
</apply>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">6</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>d_L</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>d_L_infinity</ci>
<ci>d_L</ci>
</apply>
<ci>tau_d_L</ci>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel_f_gate">
<variable initial_value="0.98651" name="f_L" public_interface="out" units="dimensionless"/>
<variable name="alpha_f_L" units="per_second"/>
<variable name="beta_f_L" units="per_second"/>
<variable name="f_L_infinity" units="dimensionless"/>
<variable name="tau_f_L" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>alpha_f_L</ci>
<apply>
<divide/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt_second">3.75</cn>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">28</cn>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">28</cn>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">4</cn>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_f_L</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">30</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">28</cn>
</apply>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">4</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_f_L</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<ci>alpha_f_L</ci>
<ci>beta_f_L</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>f_L_infinity</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">30</cn>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">5</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>f_L</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>f_L_infinity</ci>
<ci>f_L</ci>
</apply>
<ci>tau_f_L</ci>
</apply>
</apply>
</math>
</component>
<component name="T_type_Ca_channel">
<variable name="i_Ca_T" public_interface="out" units="nanoA"/>
<variable initial_value="0.02521" name="g_Ca_T" units="microS"/>
<variable initial_value="45" name="E_Ca_T" units="millivolt"/>
<variable name="time" private_interface="out" public_interface="in" units="second"/>
<variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
<variable name="d_T" private_interface="in" units="dimensionless"/>
<variable name="f_T" private_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_Ca_T</ci>
<apply>
<times/>
<ci>g_Ca_T</ci>
<ci>d_T</ci>
<ci>f_T</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Ca_T</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="T_type_Ca_channel_d_gate">
<variable initial_value="0.02012114" name="d_T" public_interface="out" units="dimensionless"/>
<variable name="alpha_d_T" units="per_second"/>
<variable name="beta_d_T" units="per_second"/>
<variable name="d_T_infinity" units="dimensionless"/>
<variable name="tau_d_T" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>alpha_d_T</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">1068</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">26.3</cn>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">30</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_d_T</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">1068</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">26.3</cn>
</apply>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">30</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_d_T</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<ci>alpha_d_T</ci>
<ci>beta_d_T</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>d_T_infinity</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">26.3</cn>
</apply>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">6</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>d_T</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>d_T_infinity</ci>
<ci>d_T</ci>
</apply>
<ci>tau_d_T</ci>
</apply>
</apply>
</math>
</component>
<component name="T_type_Ca_channel_f_gate">
<variable initial_value="0.1945111" name="f_T" public_interface="out" units="dimensionless"/>
<variable name="alpha_f_T" units="per_second"/>
<variable name="beta_f_T" units="per_second"/>
<variable name="f_T_infinity" units="dimensionless"/>
<variable name="tau_f_T" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>alpha_f_T</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">15.3</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">61.7</cn>
</apply>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">83.3</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_f_T</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">15</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">61.7</cn>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">15.38</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_f_T</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<ci>alpha_f_T</ci>
<ci>beta_f_T</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>f_T_infinity</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">61.7</cn>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">5.6</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>f_T</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>f_T_infinity</ci>
<ci>f_T</ci>
</apply>
<ci>tau_f_T</ci>
</apply>
</apply>
</math>
</component>
<component name="delayed_rectifying_potassium_current">
<variable name="i_K" public_interface="out" units="nanoA"/>
<variable name="g_K" units="microS"/>
<variable name="F_cAMP_K" units="dimensionless"/>
<variable name="cAMP" public_interface="in" units="millimolar"/>
<variable name="E_K" public_interface="in" units="millivolt"/>
<variable name="time" private_interface="out" public_interface="in" units="second"/>
<variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
<variable name="K_b" public_interface="in" units="millimolar"/>
<variable name="P_a" private_interface="in" units="dimensionless"/>
<variable name="P_i" private_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>F_cAMP_K</ci>
<apply>
<minus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.62</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2.6129</cn>
<ci>cAMP</ci>
</apply>
<apply>
<plus/>
<ci>cAMP</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" type="e-notation" cellml:units="millimolar">9<sep/>-3</cn>
</apply>
</apply>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.025</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>g_K</ci>
<apply>
<times/>
<ci>F_cAMP_K</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="microS">0.00693</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>K_b</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">1</cn>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.59</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_K</ci>
<apply>
<times/>
<ci>g_K</ci>
<ci>P_a</ci>
<ci>P_i</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="delayed_rectifying_potassium_current_P_a_gate">
<variable initial_value="0.02302278" name="P_a" public_interface="out" units="dimensionless"/>
<variable name="tau_P_a" units="second"/>
<variable name="P_a_infinity" units="dimensionless"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>P_a_infinity</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">5.1</cn>
</apply>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">7.4</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_P_a</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">17</cn>
<apply>
<exp/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.0398</cn>
<ci>V</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">2.11</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.051</cn>
</apply>
<ci>V</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>P_a</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>P_a_infinity</ci>
<ci>P_a</ci>
</apply>
<ci>tau_P_a</ci>
</apply>
</apply>
</math>
</component>
<component name="delayed_rectifying_potassium_current_P_i_gate">
<variable initial_value="0.3777728" name="P_i" public_interface="out" units="dimensionless"/>
<variable name="alpha_P_i" units="per_second"/>
<variable name="beta_P_i" units="per_second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>alpha_P_i</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">100</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.0183</cn>
</apply>
<ci>V</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_P_i</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">656</cn>
<apply>
<exp/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.00942</cn>
<ci>V</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>P_i</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_P_i</ci>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>P_i</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_P_i</ci>
<ci>P_i</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="linear_background_current">
<variable name="i_B" public_interface="out" units="nanoA"/>
<variable name="i_B_Na" public_interface="out" units="nanoA"/>
<variable name="i_B_Ca" public_interface="out" units="nanoA"/>
<variable name="i_B_K" public_interface="out" units="nanoA"/>
<variable initial_value="0.00016" name="g_B_Na" units="microS"/>
<variable initial_value="0.0000364" name="g_B_Ca" units="microS"/>
<variable initial_value="0.0000694" name="g_B_K" units="microS"/>
<variable name="E_Na" public_interface="in" units="millivolt"/>
<variable name="E_Ca" public_interface="in" units="millivolt"/>
<variable name="E_K" public_interface="in" units="millivolt"/>
<variable name="F_ACh_bNa" units="dimensionless"/>
<variable name="ACh" public_interface="in" units="millimolar"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>F_ACh_bNa</ci>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>ACh</ci>
<apply>
<plus/>
<ci>ACh</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" type="e-notation" cellml:units="millimolar">5<sep/>-1</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_B_Na</ci>
<apply>
<times/>
<ci>F_ACh_bNa</ci>
<ci>g_B_Na</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Na</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_B_Ca</ci>
<apply>
<times/>
<ci>g_B_Ca</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Ca</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_B_K</ci>
<apply>
<times/>
<ci>g_B_K</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_B</ci>
<apply>
<plus/>
<ci>i_B_Na</ci>
<ci>i_B_Ca</ci>
<ci>i_B_K</ci>
</apply>
</apply>
</math>
</component>
<component name="hyperpolarisation_activated_current">
<variable name="i_f" public_interface="out" units="nanoA"/>
<variable name="i_f_Na" public_interface="out" units="nanoA"/>
<variable name="i_f_K" public_interface="out" units="nanoA"/>
<variable initial_value="0.0067478" name="g_f_Na" units="microS"/>
<variable initial_value="0.0128821" name="g_f_K" units="microS"/>
<variable name="time" private_interface="out" public_interface="in" units="second"/>
<variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
<variable name="cAMP" private_interface="out" public_interface="in" units="millimolar"/>
<variable name="y" private_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_f_Na</ci>
<apply>
<times/>
<ci>g_f_Na</ci>
<apply>
<power/>
<ci>y</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
<apply>
<minus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">75</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_f_K</ci>
<apply>
<times/>
<ci>g_f_K</ci>
<apply>
<power/>
<ci>y</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">85</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_f</ci>
<apply>
<plus/>
<ci>i_f_Na</ci>
<ci>i_f_K</ci>
</apply>
</apply>
</math>
</component>
<component name="hyperpolarisation_activated_current_y_gate">
<variable initial_value="0.09227776" name="y" public_interface="out" units="dimensionless"/>
<variable name="y_infinity" units="dimensionless"/>
<variable name="V_half" units="millivolt"/>
<variable name="cAMP" public_interface="in" units="millimolar"/>
<variable name="tau_y" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_half</ci>
<apply>
<minus/>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">20.5</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>cAMP</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" type="e-notation" cellml:units="millimolar">3.4<sep/>-3</cn>
</apply>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" type="e-notation" cellml:units="millimolar">5<sep/>-4</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">78.56</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>y_infinity</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>V</ci>
<ci>V_half</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">9</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_y</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="second">1</cn>
<apply>
<plus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.6483</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">54.06</cn>
</apply>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">24.33</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">14.01055</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.7</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">60</cn>
</apply>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">5.5</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>y</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>y_infinity</ci>
<ci>y</ci>
</apply>
<ci>tau_y</ci>
</apply>
</apply>
</math>
</component>
<component name="sodium_potassium_pump">
<variable name="i_NaK" public_interface="out" units="nanoA"/>
<variable initial_value="5.46" name="K_m_Na" units="millimolar"/>
<variable initial_value="0.621" name="K_m_K" units="millimolar"/>
<variable initial_value="0.2192" name="i_NaK_max" units="nanoA"/>
<variable name="F_cAMP_NaK" units="dimensionless"/>
<variable name="cAMP" public_interface="in" units="millimolar"/>
<variable name="Na_i" public_interface="in" units="millimolar"/>
<variable name="K_c" public_interface="in" units="millimolar"/>
<variable name="Ca_i" public_interface="in" units="millimolar"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>F_cAMP_NaK</ci>
<apply>
<plus/>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.6</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>cAMP</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" type="e-notation" cellml:units="millimolar">3.75<sep/>-3</cn>
</apply>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" type="e-notation" cellml:units="millimolar">1.5<sep/>-4</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.99</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>i_NaK</ci>
<piecewise>
<piece>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>F_cAMP_NaK</ci>
</apply>
<ci>i_NaK_max</ci>
<apply>
<power/>
<apply>
<divide/>
<ci>Na_i</ci>
<apply>
<plus/>
<ci>K_m_Na</ci>
<ci>Na_i</ci>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
<apply>
<power/>
<apply>
<divide/>
<ci>K_c</ci>
<apply>
<plus/>
<ci>K_m_K</ci>
<ci>K_c</ci>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.6</cn>
</apply>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.5</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">60</cn>
</apply>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">40</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<lt/>
<ci>Ca_i</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">0.00015</cn>
</apply>
</piece>
<otherwise>
<apply>
<divide/>
<apply>
<times/>
<ci>F_cAMP_NaK</ci>
<ci>i_NaK_max</ci>
<apply>
<power/>
<apply>
<divide/>
<ci>Na_i</ci>
<apply>
<plus/>
<ci>K_m_Na</ci>
<ci>Na_i</ci>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
<apply>
<power/>
<apply>
<divide/>
<ci>K_c</ci>
<apply>
<plus/>
<ci>K_m_K</ci>
<ci>K_c</ci>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.6</cn>
</apply>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.5</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">60</cn>
</apply>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">40</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<component name="calcium_pump_current">
<variable name="i_Ca_P" public_interface="out" units="nanoA"/>
<variable initial_value="0.02869" name="i_Ca_P_max" units="nanoA"/>
<variable name="Ca_i" public_interface="in" units="millimolar"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_Ca_P</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>i_Ca_P_max</ci>
<ci>Ca_i</ci>
</apply>
<apply>
<plus/>
<ci>Ca_i</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">0.0004</cn>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sodium_calcium_pump">
<variable name="i_NaCa" public_interface="out" units="nanoA"/>
<variable initial_value="0.00001248" name="K_NaCa" units="nanoA"/>
<variable initial_value="0.0001" name="d_NaCa" units="dimensionless"/>
<variable initial_value="0.5" name="gamma" units="dimensionless"/>
<variable name="Na_i" public_interface="in" units="millimolar"/>
<variable name="Na_c" public_interface="in" units="millimolar"/>
<variable name="Ca_i" public_interface="in" units="millimolar"/>
<variable name="Ca_c" public_interface="in" units="millimolar"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<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>
<power/>
<ci>Na_i</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
<ci>Ca_c</ci>
<apply>
<exp/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.03743</cn>
<ci>V</ci>
<ci>gamma</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<power/>
<ci>Na_c</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
<ci>Ca_i</ci>
<apply>
<exp/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.03743</cn>
<ci>V</ci>
<apply>
<minus/>
<ci>gamma</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar_4">1</cn>
<apply>
<times/>
<ci>d_NaCa</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>Ca_i</ci>
<apply>
<power/>
<ci>Na_c</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
</apply>
<apply>
<times/>
<ci>Ca_c</ci>
<apply>
<power/>
<ci>Na_i</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="muscarinic_potassium_current">
<variable name="i_K_ACh" public_interface="out" units="nanoA"/>
<variable name="I_K_ACh" units="nanoA"/>
<variable name="ACh" public_interface="in" units="millimolar"/>
<variable name="g_K_ACh" units="microS"/>
<variable initial_value="7.833e-3" name="g_K_ACh_base" units="microS"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="E_K" public_interface="in" units="millivolt"/>
<variable name="P_M2_KACh" units="dimensionless"/>
<variable initial_value="0" name="a" units="dimensionless"/>
<variable name="alpha_a" units="per_second"/>
<variable name="beta_a" units="per_second"/>
<variable name="f_Vagal" public_interface="in" units="per_second"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_K_ACh</ci>
<apply>
<times/>
<ci>a</ci>
<ci>I_K_ACh</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>a</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>beta_a</ci>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>a</ci>
</apply>
</apply>
<apply>
<times/>
<ci>alpha_a</ci>
<ci>a</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_a</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">12.32</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">0.0042</cn>
<ci>ACh</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>alpha_a</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">17</cn>
<apply>
<exp/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.0133</cn>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">40</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>I_K_ACh</ci>
<apply>
<times/>
<ci>g_K_ACh</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>g_K_ACh</ci>
<apply>
<times/>
<ci>P_M2_KACh</ci>
<ci>g_K_ACh_base</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>P_M2_KACh</ci>
<piecewise>
<piece>
<apply>
<minus/>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.026</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>f_Vagal</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">11.05</cn>
</apply>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">7.5095</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.99</cn>
</apply>
<apply>
<and/>
<apply>
<lt/>
<ci>f_Vagal</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">100</cn>
</apply>
<apply>
<gt/>
<ci>f_Vagal</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">25</cn>
</apply>
</apply>
</piece>
<otherwise>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.0006</cn>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<component name="intracellular_concentrations_and_buffer_equations">
<variable cmeta:id="intracellular_concentrations_and_buffer_equations_Na_i" initial_value="9.701621" name="Na_i" public_interface="out" units="millimolar"/>
<variable cmeta:id="intracellular_concentrations_and_buffer_equations_Ca_i" initial_value="3.787018e-4" name="Ca_i" public_interface="out" units="millimolar"/>
<variable cmeta:id="intracellular_concentrations_and_buffer_equations_K_i" initial_value="1.407347e2" name="K_i" public_interface="out" units="millimolar"/>
<variable cmeta:id="intracellular_concentrations_and_buffer_equations_Ca_Calmod" initial_value="0.1411678" name="Ca_Calmod" units="dimensionless"/>
<variable cmeta:id="intracellular_concentrations_and_buffer_equations_Ca_Trop" initial_value="0.07331396" name="Ca_Trop" units="dimensionless"/>
<variable initial_value="0.7618549" name="Ca_Mg_Trop" units="dimensionless"/>
<variable initial_value="0.2097049" name="Mg_Mg_Trop" units="dimensionless"/>
<variable name="phi_C" units="per_second"/>
<variable name="phi_TC" units="per_second"/>
<variable name="phi_TMgC" units="per_second"/>
<variable name="phi_TMgM" units="per_second"/>
<variable name="phi_B" units="millimolar_per_second"/>
<variable initial_value="2.5" name="Mg_i" units="millimolar"/>
<variable name="F_C" units="millimolar_per_second"/>
<variable name="F_TC" units="millimolar_per_second"/>
<variable name="F_TMgC" units="millimolar_per_second"/>
<variable name="Vol" public_interface="in" units="mm_cubed"/>
<variable name="V_i" public_interface="out" units="mm_cubed"/>
<variable name="i_NaK" public_interface="in" units="nanoA"/>
<variable name="i_NaCa" public_interface="in" units="nanoA"/>
<variable name="i_B_Na" public_interface="in" units="nanoA"/>
<variable name="i_f_Na" public_interface="in" units="nanoA"/>
<variable name="i_Na" public_interface="in" units="nanoA"/>
<variable name="i_K" public_interface="in" units="nanoA"/>
<variable name="i_B_K" public_interface="in" units="nanoA"/>
<variable name="i_f_K" public_interface="in" units="nanoA"/>
<variable name="i_Ca_L" public_interface="in" units="nanoA"/>
<variable name="i_Ca_T" public_interface="in" units="nanoA"/>
<variable name="i_Ca_P" public_interface="in" units="nanoA"/>
<variable name="i_B_Ca" public_interface="in" units="nanoA"/>
<variable name="i_up" public_interface="in" units="nanoA"/>
<variable name="i_rel" public_interface="in" units="nanoA"/>
<variable name="F" public_interface="in" units="coulomb_per_mole"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_i</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.465</cn>
<ci>Vol</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>phi_C</ci>
<apply>
<minus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millimolar_second">129000</cn>
<ci>Ca_i</ci>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>Ca_Calmod</ci>
</apply>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">307</cn>
<ci>Ca_Calmod</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_Calmod</ci>
</apply>
<ci>phi_C</ci>
</apply>
<apply>
<eq/>
<ci>phi_TC</ci>
<apply>
<minus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millimolar_second">50500</cn>
<ci>Ca_i</ci>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>Ca_Trop</ci>
</apply>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">252</cn>
<ci>Ca_Trop</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_Trop</ci>
</apply>
<ci>phi_TC</ci>
</apply>
<apply>
<eq/>
<ci>phi_TMgC</ci>
<apply>
<minus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millimolar_second">129000</cn>
<ci>Ca_i</ci>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<ci>Ca_Mg_Trop</ci>
<ci>Mg_Mg_Trop</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">4.25</cn>
<ci>Ca_Mg_Trop</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_Mg_Trop</ci>
</apply>
<ci>phi_TMgC</ci>
</apply>
<apply>
<eq/>
<ci>phi_TMgM</ci>
<apply>
<minus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millimolar_second">1290</cn>
<ci>Mg_i</ci>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<ci>Ca_Mg_Trop</ci>
<ci>Mg_Mg_Trop</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">429</cn>
<ci>Mg_Mg_Trop</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Mg_Mg_Trop</ci>
</apply>
<ci>phi_TMgM</ci>
</apply>
<apply>
<eq/>
<ci>F_C</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">0.09</cn>
<ci>phi_C</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>F_TC</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">0.031</cn>
<ci>phi_TC</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>F_TMgC</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">0.062</cn>
<ci>phi_TMgC</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>phi_B</ci>
<apply>
<plus/>
<ci>F_C</ci>
<ci>F_TC</ci>
<ci>F_TMgC</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Na_i</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
<ci>i_NaK</ci>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
<ci>i_NaCa</ci>
</apply>
<ci>i_B_Na</ci>
<ci>i_f_Na</ci>
<ci>i_Na</ci>
</apply>
</apply>
<apply>
<times/>
<ci>F</ci>
<ci>V_i</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>K_i</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>i_NaK</ci>
</apply>
<apply>
<plus/>
<ci>i_K</ci>
<ci>i_f_K</ci>
<ci>i_B_K</ci>
</apply>
</apply>
<apply>
<times/>
<ci>F</ci>
<ci>V_i</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_i</ci>
</apply>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>i_NaCa</ci>
</apply>
<ci>i_rel</ci>
</apply>
<apply>
<plus/>
<ci>i_Ca_L</ci>
<ci>i_Ca_T</ci>
<ci>i_Ca_P</ci>
<ci>i_B_Ca</ci>
<ci>i_up</ci>
</apply>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>V_i</ci>
<ci>F</ci>
</apply>
</apply>
<ci>phi_B</ci>
</apply>
</apply>
</math>
</component>
<component name="cleft_space_equations">
<variable cmeta:id="cleft_space_equations_Na_c" initial_value="139.9988" name="Na_c" public_interface="out" units="millimolar"/>
<variable cmeta:id="cleft_space_equations_Ca_c" initial_value="2.00474" name="Ca_c" public_interface="out" units="millimolar"/>
<variable cmeta:id="cleft_space_equations_K_c" initial_value="5.389014" name="K_c" public_interface="out" units="millimolar"/>
<variable initial_value="5.4" name="K_b" public_interface="out" units="millimolar"/>
<variable initial_value="140" name="Na_b" units="millimolar"/>
<variable initial_value="2" name="Ca_b" units="millimolar"/>
<variable initial_value="3.497e-6" name="Vol" public_interface="out" units="mm_cubed"/>
<variable name="V_c" units="mm_cubed"/>
<variable initial_value="0.01" name="tau_p" units="second"/>
<variable name="i_NaK" public_interface="in" units="nanoA"/>
<variable name="i_NaCa" public_interface="in" units="nanoA"/>
<variable name="i_B_Na" public_interface="in" units="nanoA"/>
<variable name="i_f_Na" public_interface="in" units="nanoA"/>
<variable name="i_Na" public_interface="in" units="nanoA"/>
<variable name="i_K" public_interface="in" units="nanoA"/>
<variable name="i_B_K" public_interface="in" units="nanoA"/>
<variable name="i_f_K" public_interface="in" units="nanoA"/>
<variable name="i_Ca_L" public_interface="in" units="nanoA"/>
<variable name="i_Ca_T" public_interface="in" units="nanoA"/>
<variable name="i_Ca_P" public_interface="in" units="nanoA"/>
<variable name="i_B_Ca" public_interface="in" units="nanoA"/>
<variable name="F" public_interface="in" units="coulomb_per_mole"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_c</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.136</cn>
<ci>Vol</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Na_c</ci>
</apply>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<minus/>
<ci>Na_b</ci>
<ci>Na_c</ci>
</apply>
<ci>tau_p</ci>
</apply>
<apply>
<divide/>
<apply>
<plus/>
<ci>i_Na</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
<ci>i_NaCa</ci>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
<ci>i_NaK</ci>
</apply>
<ci>i_B_Na</ci>
<ci>i_f_Na</ci>
</apply>
<apply>
<times/>
<ci>F</ci>
<ci>V_c</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>K_c</ci>
</apply>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<minus/>
<ci>K_b</ci>
<ci>K_c</ci>
</apply>
<ci>tau_p</ci>
</apply>
<apply>
<divide/>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
<ci>i_NaK</ci>
</apply>
<ci>i_K</ci>
<ci>i_B_K</ci>
<ci>i_f_K</ci>
</apply>
<apply>
<times/>
<ci>F</ci>
<ci>V_c</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_c</ci>
</apply>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<minus/>
<ci>Ca_b</ci>
<ci>Ca_c</ci>
</apply>
<ci>tau_p</ci>
</apply>
<apply>
<divide/>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
<ci>i_NaCa</ci>
</apply>
<ci>i_Ca_L</ci>
<ci>i_Ca_T</ci>
<ci>i_Ca_P</ci>
<ci>i_B_Ca</ci>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>F</ci>
<ci>V_c</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="SR_Ca_uptake_and_release">
<variable cmeta:id="SR_Ca_uptake_and_release_i_rel" name="i_rel" public_interface="out" units="nanoA"/>
<variable cmeta:id="SR_Ca_uptake_and_release_i_up" name="i_up" public_interface="out" units="nanoA"/>
<variable initial_value="16.95311" name="Ca_up" units="millimolar"/>
<variable initial_value="0.08" name="alpha_up" units="nanoA"/>
<variable initial_value="0.072" name="beta_up" units="nanoA"/>
<variable initial_value="16.85024" name="Ca_rel" units="millimolar"/>
<variable initial_value="0.5" name="alpha_rel" units="nanoA_per_millimolar"/>
<variable cmeta:id="SR_Ca_uptake_and_release_i_tr" name="i_tr" units="nanoA"/>
<variable name="K1" units="dimensionless"/>
<variable name="K2" units="millimolar"/>
<variable initial_value="0.00005" name="k_cyca" units="millimolar"/>
<variable initial_value="0.9" name="k_xcs" units="dimensionless"/>
<variable initial_value="22" name="k_SRCa" units="millimolar"/>
<variable initial_value="0.004" name="k_rel" units="millimolar"/>
<variable name="r_act" units="per_second"/>
<variable name="r_inact" units="per_second"/>
<variable initial_value="0.9528726" name="Ca_Calse" units="dimensionless"/>
<variable name="phi_Calse" units="per_second"/>
<variable initial_value="0.1133251" name="F1" units="dimensionless"/>
<variable initial_value="0.0007594214" name="F2" units="dimensionless"/>
<variable initial_value="0.8859153" name="F3" units="dimensionless"/>
<variable name="V_i" public_interface="in" units="mm_cubed"/>
<variable name="V_up" units="mm_cubed"/>
<variable name="V_rel" units="mm_cubed"/>
<variable name="Ca_i" public_interface="in" units="millimolar"/>
<variable name="F" public_interface="in" units="coulomb_per_mole"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_up</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.01166</cn>
<ci>V_i</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>V_rel</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.001296</cn>
<ci>V_i</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>K1</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>k_cyca</ci>
<ci>k_xcs</ci>
</apply>
<ci>k_SRCa</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>K2</ci>
<apply>
<plus/>
<ci>Ca_i</ci>
<apply>
<times/>
<ci>Ca_up</ci>
<ci>K1</ci>
</apply>
<apply>
<times/>
<ci>k_cyca</ci>
<ci>k_xcs</ci>
</apply>
<ci>k_cyca</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>r_act</ci>
<apply>
<plus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">240</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">40</cn>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.08</cn>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">240</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>Ca_i</ci>
<apply>
<plus/>
<ci>Ca_i</ci>
<ci>k_rel</ci>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>r_inact</ci>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">40</cn>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">240</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>Ca_i</ci>
<apply>
<plus/>
<ci>Ca_i</ci>
<ci>k_rel</ci>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>phi_Calse</ci>
<apply>
<minus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millimolar_second">770</cn>
<ci>Ca_rel</ci>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>Ca_Calse</ci>
</apply>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">641</cn>
<ci>Ca_Calse</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_Calse</ci>
</apply>
<ci>phi_Calse</ci>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>F1</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">0.96</cn>
<ci>F3</ci>
</apply>
<apply>
<times/>
<ci>r_act</ci>
<ci>F1</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>F2</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>r_act</ci>
<ci>F1</ci>
</apply>
<apply>
<times/>
<ci>r_inact</ci>
<ci>F2</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>F3</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>r_inact</ci>
<ci>F2</ci>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">0.96</cn>
<ci>F3</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_rel</ci>
<apply>
<times/>
<ci>alpha_rel</ci>
<apply>
<power/>
<apply>
<divide/>
<ci>F2</ci>
<apply>
<plus/>
<ci>F2</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.25</cn>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
<ci>Ca_rel</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>i_tr</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>Ca_up</ci>
<ci>Ca_rel</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>F</ci>
<ci>V_up</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="second">0.06418</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>i_up</ci>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_up</ci>
<ci>Ca_i</ci>
</apply>
<apply>
<times/>
<ci>beta_up</ci>
<ci>Ca_up</ci>
<ci>K1</ci>
</apply>
</apply>
<ci>K2</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_up</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>i_up</ci>
<ci>i_tr</ci>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>V_up</ci>
<ci>F</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_rel</ci>
</apply>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<minus/>
<ci>i_tr</ci>
<ci>i_rel</ci>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>V_rel</ci>
<ci>F</ci>
</apply>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">11.48</cn>
<ci>phi_Calse</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="reversal_potentials">
<variable name="E_Na" public_interface="out" units="millivolt"/>
<variable name="E_K" public_interface="out" units="millivolt"/>
<variable name="E_Ca" public_interface="out" units="millivolt"/>
<variable name="K_c" public_interface="in" units="millimolar"/>
<variable name="Na_c" public_interface="in" units="millimolar"/>
<variable name="K_i" public_interface="in" units="millimolar"/>
<variable name="Na_i" public_interface="in" units="millimolar"/>
<variable name="Ca_c" public_interface="in" units="millimolar"/>
<variable name="Ca_i" public_interface="in" units="millimolar"/>
<variable name="R" public_interface="in" units="joule_per_kilomole_kelvin"/>
<variable name="T" public_interface="in" units="kelvin"/>
<variable name="F" public_interface="in" units="coulomb_per_mole"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>E_Na</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
<ci>F</ci>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<ci>Na_c</ci>
<ci>Na_i</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>E_K</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
<ci>F</ci>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<ci>K_c</ci>
<ci>K_i</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>E_Ca</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.5</cn>
<ci>R</ci>
<ci>T</ci>
</apply>
<ci>F</ci>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<ci>Ca_c</ci>
<ci>Ca_i</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="cAMP_balance">
<variable initial_value="3e-3" name="cAMP" public_interface="out" units="millimolar"/>
<variable initial_value="2e-3" name="cGMP" units="millimolar"/>
<variable initial_value="0" name="Iso" units="millimolar"/>
<variable initial_value="0" name="ACh" public_interface="out" units="millimolar"/>
<variable initial_value="0.14e-3" name="Km_Iso" units="millimolar"/>
<variable initial_value="0.14e-3" name="Km_ACh" units="millimolar"/>
<variable initial_value="6" name="K_PDE" units="dimensionless"/>
<variable initial_value="8e-3" name="K_ADC" units="millimolar_per_second"/>
<variable initial_value="20" name="V_PDE" units="per_second"/>
<variable initial_value="0.02" name="P_M2_ADC" units="dimensionless"/>
<variable name="time" public_interface="in" units="second"/>
<variable initial_value="200" name="f_Vagal" public_interface="out" units="per_second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>cAMP</ci>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<minus/>
<apply>
<times/>
<ci>K_ADC</ci>
<apply>
<minus/>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>Iso</ci>
<apply>
<plus/>
<ci>Iso</ci>
<ci>Km_Iso</ci>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>P_M2_ADC</ci>
<ci>ACh</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>P_M2_ADC</ci>
<ci>ACh</ci>
</apply>
<ci>Km_ACh</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>V_PDE</ci>
<ci>cGMP</ci>
<ci>cAMP</ci>
</apply>
<apply>
<plus/>
<ci>cAMP</ci>
<apply>
<times/>
<ci>K_PDE</ci>
<ci>cGMP</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<group>
<relationship_ref relationship="containment"/>
<component_ref component="membrane">
<component_ref component="sodium_current">
<component_ref component="sodium_current_m_gate"/>
<component_ref component="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="T_type_Ca_channel">
<component_ref component="T_type_Ca_channel_d_gate"/>
<component_ref component="T_type_Ca_channel_f_gate"/>
</component_ref>
<component_ref component="delayed_rectifying_potassium_current">
<component_ref component="delayed_rectifying_potassium_current_P_a_gate"/>
<component_ref component="delayed_rectifying_potassium_current_P_i_gate"/>
</component_ref>
<component_ref component="linear_background_current"/>
<component_ref component="hyperpolarisation_activated_current">
<component_ref component="hyperpolarisation_activated_current_y_gate"/>
</component_ref>
<component_ref component="sodium_potassium_pump"/>
<component_ref component="calcium_pump_current"/>
<component_ref component="sodium_calcium_pump"/>
<component_ref component="muscarinic_potassium_current"/>
<component_ref component="intracellular_concentrations_and_buffer_equations"/>
<component_ref component="cleft_space_equations"/>
<component_ref component="SR_Ca_uptake_and_release"/>
<component_ref component="reversal_potentials"/>
<component_ref component="cAMP_balance"/>
</component_ref>
</group>
<group>
<relationship_ref relationship="encapsulation"/>
<component_ref component="sodium_current">
<component_ref component="sodium_current_m_gate"/>
<component_ref component="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="T_type_Ca_channel">
<component_ref component="T_type_Ca_channel_d_gate"/>
<component_ref component="T_type_Ca_channel_f_gate"/>
</component_ref>
<component_ref component="delayed_rectifying_potassium_current">
<component_ref component="delayed_rectifying_potassium_current_P_a_gate"/>
<component_ref component="delayed_rectifying_potassium_current_P_i_gate"/>
</component_ref>
<component_ref component="hyperpolarisation_activated_current">
<component_ref component="hyperpolarisation_activated_current_y_gate"/>
</component_ref>
</group>
<connection>
<map_components component_1="membrane" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="sodium_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="L_type_Ca_channel" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="T_type_Ca_channel" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="delayed_rectifying_potassium_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="linear_background_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="hyperpolarisation_activated_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="sodium_potassium_pump" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="calcium_pump_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="sodium_calcium_pump" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="muscarinic_potassium_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="intracellular_concentrations_and_buffer_equations" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="cleft_space_equations" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="SR_Ca_uptake_and_release" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="reversal_potentials" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="cAMP_balance" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="sodium_current"/>
<map_variables variable_1="i_Na" variable_2="i_Na"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="L_type_Ca_channel"/>
<map_variables variable_1="i_Ca_L" variable_2="i_Ca_L"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="T_type_Ca_channel"/>
<map_variables variable_1="i_Ca_T" variable_2="i_Ca_T"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="delayed_rectifying_potassium_current"/>
<map_variables variable_1="i_K" variable_2="i_K"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="linear_background_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_B" variable_2="i_B"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="hyperpolarisation_activated_current"/>
<map_variables variable_1="i_f" variable_2="i_f"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="calcium_pump_current" component_2="membrane"/>
<map_variables variable_1="i_Ca_P" variable_2="i_Ca_P"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="sodium_potassium_pump"/>
<map_variables variable_1="i_NaK" variable_2="i_NaK"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="sodium_calcium_pump"/>
<map_variables variable_1="i_NaCa" variable_2="i_NaCa"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="muscarinic_potassium_current" component_2="membrane"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_K_ACh" variable_2="i_K_ACh"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="intracellular_concentrations_and_buffer_equations"/>
<map_variables variable_1="F" variable_2="F"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="cleft_space_equations"/>
<map_variables variable_1="F" variable_2="F"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="SR_Ca_uptake_and_release"/>
<map_variables variable_1="F" variable_2="F"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="reversal_potentials"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
</connection>
<connection>
<map_components component_1="reversal_potentials" component_2="sodium_current"/>
<map_variables variable_1="E_Na" variable_2="E_Na"/>
</connection>
<connection>
<map_components component_1="intracellular_concentrations_and_buffer_equations" component_2="sodium_current"/>
<map_variables variable_1="i_Na" variable_2="i_Na"/>
</connection>
<connection>
<map_components component_1="cleft_space_equations" component_2="sodium_current"/>
<map_variables variable_1="i_Na" variable_2="i_Na"/>
<map_variables variable_1="Na_c" variable_2="Na_c"/>
</connection>
<connection>
<map_components component_1="L_type_Ca_channel" component_2="cleft_space_equations"/>
<map_variables variable_1="i_Ca_L" variable_2="i_Ca_L"/>
</connection>
<connection>
<map_components component_1="L_type_Ca_channel" component_2="intracellular_concentrations_and_buffer_equations"/>
<map_variables variable_1="i_Ca_L" variable_2="i_Ca_L"/>
</connection>
<connection>
<map_components component_1="T_type_Ca_channel" component_2="cleft_space_equations"/>
<map_variables variable_1="i_Ca_T" variable_2="i_Ca_T"/>
</connection>
<connection>
<map_components component_1="T_type_Ca_channel" component_2="intracellular_concentrations_and_buffer_equations"/>
<map_variables variable_1="i_Ca_T" variable_2="i_Ca_T"/>
</connection>
<connection>
<map_components component_1="cleft_space_equations" component_2="delayed_rectifying_potassium_current"/>
<map_variables variable_1="i_K" variable_2="i_K"/>
<map_variables variable_1="K_b" variable_2="K_b"/>
</connection>
<connection>
<map_components component_1="intracellular_concentrations_and_buffer_equations" component_2="delayed_rectifying_potassium_current"/>
<map_variables variable_1="i_K" variable_2="i_K"/>
</connection>
<connection>
<map_components component_1="reversal_potentials" component_2="delayed_rectifying_potassium_current"/>
<map_variables variable_1="E_K" variable_2="E_K"/>
</connection>
<connection>
<map_components component_1="reversal_potentials" component_2="linear_background_current"/>
<map_variables variable_1="E_Na" variable_2="E_Na"/>
<map_variables variable_1="E_Ca" variable_2="E_Ca"/>
<map_variables variable_1="E_K" variable_2="E_K"/>
</connection>
<connection>
<map_components component_1="muscarinic_potassium_current" component_2="reversal_potentials"/>
<map_variables variable_1="E_K" variable_2="E_K"/>
</connection>
<connection>
<map_components component_1="cleft_space_equations" component_2="linear_background_current"/>
<map_variables variable_1="i_B_Na" variable_2="i_B_Na"/>
<map_variables variable_1="i_B_Ca" variable_2="i_B_Ca"/>
<map_variables variable_1="i_B_K" variable_2="i_B_K"/>
</connection>
<connection>
<map_components component_1="intracellular_concentrations_and_buffer_equations" component_2="linear_background_current"/>
<map_variables variable_1="i_B_Na" variable_2="i_B_Na"/>
<map_variables variable_1="i_B_Ca" variable_2="i_B_Ca"/>
<map_variables variable_1="i_B_K" variable_2="i_B_K"/>
</connection>
<connection>
<map_components component_1="intracellular_concentrations_and_buffer_equations" component_2="hyperpolarisation_activated_current"/>
<map_variables variable_1="i_f_K" variable_2="i_f_K"/>
<map_variables variable_1="i_f_Na" variable_2="i_f_Na"/>
</connection>
<connection>
<map_components component_1="cleft_space_equations" component_2="hyperpolarisation_activated_current"/>
<map_variables variable_1="i_f_K" variable_2="i_f_K"/>
<map_variables variable_1="i_f_Na" variable_2="i_f_Na"/>
</connection>
<connection>
<map_components component_1="sodium_potassium_pump" component_2="intracellular_concentrations_and_buffer_equations"/>
<map_variables variable_1="Na_i" variable_2="Na_i"/>
<map_variables variable_1="Ca_i" variable_2="Ca_i"/>
<map_variables variable_1="i_NaK" variable_2="i_NaK"/>
</connection>
<connection>
<map_components component_1="sodium_potassium_pump" component_2="cleft_space_equations"/>
<map_variables variable_1="K_c" variable_2="K_c"/>
<map_variables variable_1="i_NaK" variable_2="i_NaK"/>
</connection>
<connection>
<map_components component_1="calcium_pump_current" component_2="cleft_space_equations"/>
<map_variables variable_1="i_Ca_P" variable_2="i_Ca_P"/>
</connection>
<connection>
<map_components component_1="calcium_pump_current" component_2="intracellular_concentrations_and_buffer_equations"/>
<map_variables variable_1="i_Ca_P" variable_2="i_Ca_P"/>
<map_variables variable_1="Ca_i" variable_2="Ca_i"/>
</connection>
<connection>
<map_components component_1="sodium_calcium_pump" component_2="intracellular_concentrations_and_buffer_equations"/>
<map_variables variable_1="Ca_i" variable_2="Ca_i"/>
<map_variables variable_1="Na_i" variable_2="Na_i"/>
<map_variables variable_1="i_NaCa" variable_2="i_NaCa"/>
</connection>
<connection>
<map_components component_1="sodium_calcium_pump" component_2="cleft_space_equations"/>
<map_variables variable_1="Ca_c" variable_2="Ca_c"/>
<map_variables variable_1="Na_c" variable_2="Na_c"/>
<map_variables variable_1="i_NaCa" variable_2="i_NaCa"/>
</connection>
<connection>
<map_components component_1="reversal_potentials" component_2="intracellular_concentrations_and_buffer_equations"/>
<map_variables variable_1="K_i" variable_2="K_i"/>
<map_variables variable_1="Na_i" variable_2="Na_i"/>
<map_variables variable_1="Ca_i" variable_2="Ca_i"/>
</connection>
<connection>
<map_components component_1="reversal_potentials" component_2="cleft_space_equations"/>
<map_variables variable_1="K_c" variable_2="K_c"/>
<map_variables variable_1="Na_c" variable_2="Na_c"/>
<map_variables variable_1="Ca_c" variable_2="Ca_c"/>
</connection>
<connection>
<map_components component_1="intracellular_concentrations_and_buffer_equations" component_2="cleft_space_equations"/>
<map_variables variable_1="Vol" variable_2="Vol"/>
</connection>
<connection>
<map_components component_1="intracellular_concentrations_and_buffer_equations" component_2="SR_Ca_uptake_and_release"/>
<map_variables variable_1="i_rel" variable_2="i_rel"/>
<map_variables variable_1="i_up" variable_2="i_up"/>
<map_variables variable_1="Ca_i" variable_2="Ca_i"/>
<map_variables variable_1="V_i" variable_2="V_i"/>
</connection>
<connection>
<map_components component_1="sodium_current" component_2="sodium_current_m_gate"/>
<map_variables variable_1="m" variable_2="m"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="sodium_current" component_2="sodium_current_h_gate"/>
<map_variables variable_1="h1" variable_2="h1"/>
<map_variables variable_1="h2" variable_2="h2"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="L_type_Ca_channel" component_2="L_type_Ca_channel_d_gate"/>
<map_variables variable_1="d_L" variable_2="d_L"/>
<map_variables variable_1="d_L_infinity" variable_2="d_L_infinity"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="L_type_Ca_channel" component_2="L_type_Ca_channel_f_gate"/>
<map_variables variable_1="f_L" variable_2="f_L"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="T_type_Ca_channel" component_2="T_type_Ca_channel_d_gate"/>
<map_variables variable_1="d_T" variable_2="d_T"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="T_type_Ca_channel" component_2="T_type_Ca_channel_f_gate"/>
<map_variables variable_1="f_T" variable_2="f_T"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="delayed_rectifying_potassium_current" component_2="delayed_rectifying_potassium_current_P_a_gate"/>
<map_variables variable_1="P_a" variable_2="P_a"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="delayed_rectifying_potassium_current" component_2="delayed_rectifying_potassium_current_P_i_gate"/>
<map_variables variable_1="P_i" variable_2="P_i"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="hyperpolarisation_activated_current" component_2="hyperpolarisation_activated_current_y_gate"/>
<map_variables variable_1="y" variable_2="y"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="cAMP" variable_2="cAMP"/>
</connection>
<connection>
<map_components component_1="L_type_Ca_channel" component_2="cAMP_balance"/>
<map_variables variable_1="cAMP" variable_2="cAMP"/>
</connection>
<connection>
<map_components component_1="delayed_rectifying_potassium_current" component_2="cAMP_balance"/>
<map_variables variable_1="cAMP" variable_2="cAMP"/>
</connection>
<connection>
<map_components component_1="hyperpolarisation_activated_current" component_2="cAMP_balance"/>
<map_variables variable_1="cAMP" variable_2="cAMP"/>
</connection>
<connection>
<map_components component_1="sodium_potassium_pump" component_2="cAMP_balance"/>
<map_variables variable_1="cAMP" variable_2="cAMP"/>
</connection>
<connection>
<map_components component_1="muscarinic_potassium_current" component_2="cAMP_balance"/>
<map_variables variable_1="ACh" variable_2="ACh"/>
<map_variables variable_1="f_Vagal" variable_2="f_Vagal"/>
</connection>
<connection>
<map_components component_1="sodium_current" component_2="cAMP_balance"/>
<map_variables variable_1="ACh" variable_2="ACh"/>
</connection>
<connection>
<map_components component_1="linear_background_current" component_2="cAMP_balance"/>
<map_variables variable_1="ACh" variable_2="ACh"/>
</connection>
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<rdf:Bag rdf:about="rdf:#d19e13e7-c8dd-4c28-bcc3-06380bf8f491">
<rdf:li>cardiac</rdf:li>
<rdf:li>signal transduction</rdf:li>
<rdf:li>sinoatrial node</rdf:li>
<rdf:li>electrophysiology</rdf:li>
</rdf:Bag>
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<rdf:Description rdf:about="#ACh_sensitive_K_current">
<cmeta:comment rdf:resource="rdf:#f52f0c0a-5613-4337-a4c5-1c9592ec92d7"/>
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<rdf:Description rdf:about="rdf:#24c3b393-788b-462a-8335-95962aaaa850">
<dcterms:modified xmlns:dcterms="http://purl.org/dc/terms/" rdf:resource="rdf:#6da77758-e06f-47be-9a78-ed6199f8dcd1"/>
<rdf:value>added cmeta:id's for some variables to allow referencing by PCEnv session</rdf:value>
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<rdf:Description rdf:about="rdf:#e8543daf-bc07-480a-ad68-2c1ae176c5e3">
<dcterms:W3CDTF xmlns:dcterms="http://purl.org/dc/terms/">2002-07-18</dcterms:W3CDTF>
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<vCard:Orgname xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">The University of Auckland</vCard:Orgname>
<vCard:Orgunit xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">The Bioengineering Institute</vCard:Orgunit>
</rdf:Description>
<rdf:Description rdf:about="rdf:#57c9b06f-baa7-4fea-83e7-eae0545c1ece">
<dcterms:modified xmlns:dcterms="http://purl.org/dc/terms/" rdf:resource="rdf:#e0ecc64f-e5e0-4928-b6e6-ba161efed972"/>
<rdf:value>This model has been validated by Penny Noble of Oxford University.</rdf:value>
<cmeta:modifier rdf:resource="rdf:#1c348d0d-7e41-4e88-9672-2952caf0697c"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#a1facdbc-b851-4a8e-aa0d-d8e2ae379e17">
<vCard:FN xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Catherine Lloyd</vCard:FN>
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<rdf:Description rdf:about="rdf:#9fe02731-09df-4e93-ada0-32981171c291">
<vCard:N xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" rdf:resource="rdf:#8595a970-b19b-492e-8acb-840dedb4f9c5"/>
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<rdf:Description rdf:about="rdf:#7b7a912a-79d5-4aaa-9a7c-df3f50fc8bad">
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<rdf:Description rdf:about="rdf:#c2473eba-e624-4238-b498-a712b4cc6fc7">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
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<rdf:Description rdf:about="rdf:#ec204f10-1965-4299-8ae6-07715447e289">
<dcterms:modified xmlns:dcterms="http://purl.org/dc/terms/" rdf:resource="rdf:#bbb0a67d-98c6-48dc-a28b-c7bd992b62f4"/>
<rdf:value>Corrected several equations.</rdf:value>
<cmeta:modifier rdf:resource="rdf:#9d92c8c9-2ae8-4669-9bf0-889b0bfec98a"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#4c84c820-8495-42b7-97e6-e3570cc58a74">
<rdf:value>The effects of ACh and Iso on i_Ca_L and i_K are produced indirectly via the cAMP-dependent modulation of L-type Ca2+ and K+ channel
conductance (g_Ca_L and g_K) respectively.</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#667e6f48-f54f-4120-aee1-945d7eab48d9">
<vCard:Given xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Catherine</vCard:Given>
<vCard:Family xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Lloyd</vCard:Family>
<vCard:Other xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#b2ead0e0-589d-492a-8a9b-bf395dcf69c4">
<dcterms:W3CDTF xmlns:dcterms="http://purl.org/dc/terms/">2002-07-18</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#22d10804-1ba9-422e-8f07-4c03f8bfe667">
<dcterms:modified xmlns:dcterms="http://purl.org/dc/terms/" rdf:resource="rdf:#6713501e-5de1-47b7-b5d0-91f87b5a430f"/>
<rdf:value>Corrected some units.</rdf:value>
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</rdf:Description>
<rdf:Description rdf:about="#sodium_potassium_pump">
<cmeta:comment rdf:resource="rdf:#61e6be0d-4bfd-490b-af36-69a701824ac0"/>
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<vCard:Given xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Catherine</vCard:Given>
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<vCard:Other xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">May</vCard:Other>
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<rdf:Description rdf:about="#sodium_current">
<cmeta:comment rdf:resource="rdf:#a148579a-13ad-4ce5-ab34-c5796d608ad7"/>
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<ns7:boundIntervals xmlns:ns7="http://www.cellml.org/metadata/simulation/1.0#" rdf:resource="rdf:#$5yM4i3"/>
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<rdf:Description rdf:about="rdf:#35c72023-32e1-4137-82db-21b4556c8c10">
<dcterms:modified xmlns:dcterms="http://purl.org/dc/terms/" rdf:resource="rdf:#b2ead0e0-589d-492a-8a9b-bf395dcf69c4"/>
<rdf:value>Added more metadata.</rdf:value>
<cmeta:modifier rdf:resource="rdf:#9fe02731-09df-4e93-ada0-32981171c291"/>
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<rdf:Description rdf:about="rdf:#6713501e-5de1-47b7-b5d0-91f87b5a430f">
<dcterms:W3CDTF xmlns:dcterms="http://purl.org/dc/terms/">2002-02-28</dcterms:W3CDTF>
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<rdf:Description rdf:about="rdf:#6da77758-e06f-47be-9a78-ed6199f8dcd1">
<dcterms:W3CDTF xmlns:dcterms="http://purl.org/dc/terms/">2007-12-19T13:48:43+13:00</dcterms:W3CDTF>
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<rdf:Description rdf:about="rdf:#ccea4e26-cdc2-49e2-b9ea-15245fefb912">
<dc:creator xmlns:dc="http://purl.org/dc/elements/1.1/" rdf:resource="rdf:#a1facdbc-b851-4a8e-aa0d-d8e2ae379e17"/>
<rdf:value>Below is a CellML description of Demir et al's 1999 mathematical model of parasympathetic modulation of sinoatrial node (SAN) pacemaker activity in a rabbit heart. Based on experimental data, this model is a development of their earlier model of the single rabbit SAN cell (1994). Modifications have been made enabling it to mimic the important effects of the second-messenger cAMP and to simulate the response of SAN cells to the neurotransmitter acetylcholine (ACh) and isoprenaline (Iso).</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#fdddd685-7dad-464c-960d-b9869185c19c">
<bqs:subject_type xmlns:bqs="http://www.cellml.org/bqs/1.0#">keyword</bqs:subject_type>
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<vCard:Given xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">John</vCard:Given>
<vCard:Family xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Clark</vCard:Family>
<vCard:Other xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">W</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#9d35de97-b0e8-4b67-bd1c-cbce96ab70c3">
<vCard:Given xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Semahat</vCard:Given>
<vCard:Family xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Demir</vCard:Family>
<vCard:Other xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">S</vCard:Other>
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<rdf:Description rdf:about="rdf:#cbb64d35-321e-4a06-9083-a2ce5bee5a76">
<rdf:type rdf:resource="http://imc.org/vCard/3.0#internet"/>
<rdf:value>c.lloyd@auckland.ac.nz</rdf:value>
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<rdf:Description rdf:about="rdf:#a7d225a0-b87b-4275-a28f-e2e2393acfa3">
<dcterms:W3CDTF xmlns:dcterms="http://purl.org/dc/terms/">2005-04-25</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#d2719631-8fd3-4cc7-8124-48eb39dc8215">
<rdf:value>i_f is modulated via a direct effect of cAMP on the
voltage-dependence of its steady-state activation variable y.</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#$6yM4i3">
<ns7:endingValue xmlns:ns7="http://www.cellml.org/metadata/simulation/1.0#">2</ns7:endingValue>
<ns7:nonstandard-pointDensity xmlns:ns7="http://www.cellml.org/metadata/simulation/1.0#">100000</ns7:nonstandard-pointDensity>
<ns7:maximumStepSize xmlns:ns7="http://www.cellml.org/metadata/simulation/1.0#">0.1</ns7:maximumStepSize>
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<rdf:Description rdf:about="rdf:#5dd9a12d-084e-4b4d-946e-0d1603bf6586">
<vCard:Given xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Catherine</vCard:Given>
<vCard:Family xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Lloyd</vCard:Family>
<vCard:Other xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#4ac262c5-fb67-4f03-8863-8430c0142c0c">
<dcterms:modified xmlns:dcterms="http://purl.org/dc/terms/" rdf:resource="rdf:#a7d225a0-b87b-4275-a28f-e2e2393acfa3"/>
<rdf:value>Changed equivalent to eq in apply id line.</rdf:value>
<cmeta:modifier rdf:resource="rdf:#9dd209e8-3623-4e12-af33-e9c9e72ef204"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#f52f0c0a-5613-4337-a4c5-1c9592ec92d7">
<rdf:value>ACh has a direct stimulatory affect on the ACh-sensitive potassium
channel. The G-protein-mediated, direct affect of ACh on i_K_ACh
occurs via the extrajunctional M2/K_ACh muscarinic receptor. This
channel has a single gating variable a.</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#74e107aa-e69e-4b03-8323-63a8dd374f64">
<dc:subject xmlns:dc="http://purl.org/dc/elements/1.1/" rdf:resource="rdf:#fdddd685-7dad-464c-960d-b9869185c19c"/>
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</rdf:Description>
<rdf:Description rdf:about="#T_type_Ca_channel">
<cmeta:comment rdf:resource="rdf:#f530ff7d-c7ba-4b1b-83c3-c51de5c7a062"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#ca3985aa-b574-4adf-8b57-052b2b5d1681">
<vCard:ORG xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" rdf:resource="rdf:#24d9a681-3baf-4508-9533-c2239be1c593"/>
<vCard:EMAIL xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" rdf:resource="rdf:#cbb64d35-321e-4a06-9083-a2ce5bee5a76"/>
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<rdf:Description rdf:about="rdf:#417ffd9b-808c-4862-a98c-d373d6b1cda6">
<dcterms:W3CDTF xmlns:dcterms="http://purl.org/dc/terms/">2003-04-05</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#aa958ea1-adc6-474a-a037-df3c2ddbc52d">
<vCard:FN xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">James Lawson</vCard:FN>
</rdf:Description>
<rdf:Description rdf:about="rdf:#c54bd8a5-a410-4c49-82c9-76908b85ff94">
<dc:creator xmlns:dc="http://purl.org/dc/elements/1.1/" rdf:resource="rdf:#aa958ea1-adc6-474a-a037-df3c2ddbc52d"/>
<rdf:value>This model has been validated by Penny Noble of Oxford University and is known to run in COR and PCEnv. A PCEnv session file is also associated with this version. Model curated by Penny Noble using Demir 1994 Oxsoft Heart model code and Demir 1999 paper.</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#L_type_Ca_channel">
<cmeta:comment rdf:resource="rdf:#4c84c820-8495-42b7-97e6-e3570cc58a74"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#70cc5358-26a2-4176-a99b-07c1a84dc764">
<dcterms:W3CDTF xmlns:dcterms="http://purl.org/dc/terms/">1999-06-01</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#8595a970-b19b-492e-8acb-840dedb4f9c5">
<vCard:Given xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Catherine</vCard:Given>
<vCard:Family xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Lloyd</vCard:Family>
<vCard:Other xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#f530ff7d-c7ba-4b1b-83c3-c51de5c7a062">
<rdf:value>The T-type calcium channel has two gates, an activation gate d_T
and an inactivation gate f_T.</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#b77ca23e-cadf-4f3c-892b-a1740c6a20b3">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
<vCard:N xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" rdf:resource="rdf:#4b82cb56-55dc-4d6a-a414-4934078d22b1"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#61e6be0d-4bfd-490b-af36-69a701824ac0">
<rdf:value>The effects of Iso on i_NaK may be species dependent as it has been observed that Iso directly stimulates Na+-K+-ATPase activity in
rabbit ventricular myocytes (Desilets and Baumgarten, 1986), but
indirectly stimulates i_NaK in guinea pig ventricular myocytes via
a PKA phosphorylation step (Gao et al. 1992, 1994). In the absence of any quantitative evidence, in this model Demir et al. have
assumed that cAMP directly stimulates i_NaK in the rabbit SAN cell
and that this cAMP dependency may be modelled by the equations
below.</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#fd9c4d2c-b624-4de1-9203-73e936aea096">
<dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">American Journal of Physiology</dc:title>
</rdf:Description>
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<rdf:value>Changed the model name so the model loads in the database easier.</rdf:value>
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<dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">Parasympathetic modulation of sinoatrial node pacemaker activity in rabbit heart: a unifying model</dc:title>
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