- Author:
- neilstephen2001 <npar276@aucklanduni.ac.nz>
- Date:
- 2021-01-24 21:37:35+13:00
- Desc:
- adding OMEX archives to workspace
- Permanent Source URI:
- http://models.cellml.org/workspace/7f1/rawfile/110f9ba31e34b7499c8d02e13a6b9984351c0e8f/keizer_levine_1996/model/keizer_levine_1996.cellml
<?xml version="1.0" encoding="UTF-8"?>
<model xmlns="http://www.cellml.org/cellml/1.1#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:semsim="http://www.bhi.washington.edu/SemSim#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" name="keizer_levine_1996" cmeta:id="keizer_model_1996">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>RyR Adaptation and Ca2+ Oscillations</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
The ryanodine receptor (RyR) from cardiac cells and skeletal muscle undergoes a Ca
<superscript>2+</superscript>
-dependent process called adaptation. Adaptation occurs during the slow, spontaneous decrease in the open probability of a channel after it has been rapidly activated by a pulse of cytosolic calcium ([Ca
<superscript>2+</superscript>
]
<subscript>i</subscript>
). RyR activation occurs within milliseconds, whereas inactivation occurs on a timescale of a few seconds. The RyR is said to have "adapted" during inactivation because a subsequent increase in [Ca
<superscript>2+</superscript>
]
<subscript>i</subscript>
produces a nearly identical rise in the open probability.
</para>
<para>
In their 1996 paper, Joel Keizer and Leslie Levine develop a simplified model that mimics the "adaptation" of the RyR, and they investigate its significance for Ca
<superscript>2+</superscript>
-induced Ca
<superscript>2+</superscript>
release and Ca
<superscript>2+</superscript>
oscillations in cardiac cells. The mechanism used to mimic adaptation of the RyR is shown schematically in
<xref linkend="fig_reaction_diagram" />
below. States C1 and C2 are closed states and O1 and O2 are open states. Transitions from C1 to O1 and from O1 to O2 are assumed to be Ca
<superscript>2+</superscript>
-dependent. These steps correspond to the phenomenon of Ca
<superscript>2+</superscript>
-induced Ca
<superscript>2+</superscript>
release (CICR). To analyse the mechanism in
<xref linkend="fig_reaction_diagram" />
, Keizer and Levine translated the schematic diagram into kinetic equations. In addition, they test these equations in a closed-cell kinetic model, and they find that RyR adaptation can cause Ca
<superscript>2+</superscript>
oscillations. However, in an open-cell, CICR, not RyR adaptation, produces Ca
<superscript>2+</superscript>
oscillations.
</para>
<para>The complete original paper reference is cited below:</para>
<para>
<ulink url="http://www.biophysj.org/cgi/content/abstract/71/6/3477">
Ryanodine Receptor Adaptation and Ca
<superscript>2+</superscript>
-Induced Ca
<superscript>2+</superscript>
Release-Dependent Ca
<superscript>2+</superscript>
Oscillations
</ulink>
, Joel Keizer and Leslie Levine, 1996,
<ulink url="http://www.biophysj.org/">
<emphasis>Biophysical Journal</emphasis>
</ulink>
, 71, 3477-3487.
<ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8968617&dopt=Abstract">PubMed ID: 8968617</ulink>
</para>
<para>
The raw CellML description of the kinetic model of cardiac RyR adaptation can be downloaded in various formats as described in
<xref linkend="sec_download_this_model" />
.
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>Schematic diagram of the RyR model</title>
</objectinfo>
<imagedata fileref="keizer_1996.png" />
</imageobject>
</mediaobject>
<caption>
Schematic diagram of transitions among the four states of the RyR used to describe adaptation. States C1 and C2 are closed states and O1 and O2 represent open states, assumed to have the same single-channel conductance. The
<emphasis>k</emphasis>
are rate constants: only steps
<emphasis>a</emphasis>
and
<emphasis>b</emphasis>
are Ca
<superscript>2+</superscript>
dependent.
</caption>
</informalfigure>
</sect1>
</article>
</documentation>
<units name="flux">
<unit units="micromolar" />
<unit exponent="-1.0" units="second" />
</units>
<units name="micromolar_4">
<unit exponent="4.0" units="micromolar" />
</units>
<units name="micromolar_3">
<unit exponent="3.0" units="micromolar" />
</units>
<units name="forth_order_rate_constant">
<unit exponent="-1.0" units="second" />
<unit exponent="-3.0" units="micromolar" />
</units>
<units name="first_order_rate_constant">
<unit exponent="-1.0" units="second" />
</units>
<units name="micromolar">
<unit exponent="-1.0" units="litre" />
<unit prefix="micro" units="mole" />
</units>
<units name="second_order_rate_constant">
<unit exponent="-1.0" units="second" />
<unit exponent="-1.0" units="micromolar" />
</units>
<units name="fifth_order_rate_constant">
<unit exponent="-4.0" units="micromolar" />
<unit exponent="-1.0" units="second" />
</units>
<component name="environment">
<variable cmeta:id="environment.time" name="time" public_interface="out" units="second" />
</component>
<component name="P_C1" cmeta:id="P_C1">
<variable cmeta:id="P_C1.P_C1" name="P_C1" public_interface="out" units="dimensionless" />
<variable cmeta:id="P_C1.n" name="n" public_interface="in" units="dimensionless" />
<variable cmeta:id="P_C1.time" name="time" public_interface="in" units="second" />
<variable cmeta:id="P_C1.Cai" name="Cai" public_interface="in" units="micromolar" />
<variable cmeta:id="P_C1.ka" name="ka" public_interface="in" units="fifth_order_rate_constant" />
<variable cmeta:id="P_C1.ka_" name="ka_" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="P_C1.P_O1" name="P_O1" public_interface="in" units="dimensionless" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>P_C1</ci>
</apply>
<apply>
<plus />
<apply>
<minus />
<apply>
<times />
<ci>ka</ci>
<apply>
<power />
<ci>Cai</ci>
<ci>n</ci>
</apply>
<ci>P_C1</ci>
</apply>
</apply>
<apply>
<times />
<ci>ka_</ci>
<ci>P_O1</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="P_O1" cmeta:id="P_O1">
<variable cmeta:id="P_O1.P_O1" name="P_O1" public_interface="out" units="dimensionless" />
<variable cmeta:id="P_O1.n" name="n" public_interface="in" units="dimensionless" />
<variable cmeta:id="P_O1.m" name="m" public_interface="in" units="dimensionless" />
<variable cmeta:id="P_O1.time" name="time" public_interface="in" units="second" />
<variable cmeta:id="P_O1.Cai" name="Cai" public_interface="in" units="micromolar" />
<variable cmeta:id="P_O1.ka" name="ka" public_interface="in" units="fifth_order_rate_constant" />
<variable cmeta:id="P_O1.ka_" name="ka_" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="P_O1.kb" name="kb" public_interface="in" units="forth_order_rate_constant" />
<variable cmeta:id="P_O1.kb_" name="kb_" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="P_O1.kc" name="kc" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="P_O1.kc_" name="kc_" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="P_O1.P_C1" name="P_C1" public_interface="in" units="dimensionless" />
<variable cmeta:id="P_O1.P_C2" name="P_C2" public_interface="in" units="dimensionless" />
<variable cmeta:id="P_O1.P_O2" name="P_O2" public_interface="in" units="dimensionless" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>P_O1</ci>
</apply>
<apply>
<plus />
<apply>
<times />
<ci>ka</ci>
<apply>
<power />
<ci>Cai</ci>
<ci>n</ci>
</apply>
<ci>P_C1</ci>
</apply>
<apply>
<minus />
<apply>
<plus />
<apply>
<times />
<ci>ka_</ci>
<ci>P_O1</ci>
</apply>
<apply>
<times />
<ci>kb</ci>
<apply>
<power />
<ci>Cai</ci>
<ci>m</ci>
</apply>
<ci>P_O1</ci>
</apply>
</apply>
</apply>
<apply>
<times />
<ci>kb_</ci>
<ci>P_O2</ci>
</apply>
<apply>
<minus />
<apply>
<times />
<ci>kc</ci>
<ci>P_O1</ci>
</apply>
</apply>
<apply>
<times />
<ci>kc_</ci>
<ci>P_C2</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="P_O2" cmeta:id="P_O2">
<variable cmeta:id="P_O2.P_O2" name="P_O2" public_interface="out" units="dimensionless" />
<variable cmeta:id="P_O2.m" name="m" public_interface="in" units="dimensionless" />
<variable cmeta:id="P_O2.time" name="time" public_interface="in" units="second" />
<variable cmeta:id="P_O2.Cai" name="Cai" public_interface="in" units="micromolar" />
<variable cmeta:id="P_O2.kb" name="kb" public_interface="in" units="forth_order_rate_constant" />
<variable cmeta:id="P_O2.kb_" name="kb_" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="P_O2.P_O1" name="P_O1" public_interface="in" units="dimensionless" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>P_O2</ci>
</apply>
<apply>
<plus />
<apply>
<minus />
<apply>
<times />
<ci>kb</ci>
<apply>
<power />
<ci>Cai</ci>
<ci>m</ci>
</apply>
<ci>P_O1</ci>
</apply>
</apply>
<apply>
<times />
<ci>kb_</ci>
<ci>P_O2</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="P_C2" cmeta:id="P_C2">
<variable cmeta:id="P_C2.P_C2" name="P_C2" public_interface="out" units="dimensionless" />
<variable cmeta:id="P_C2.time" name="time" public_interface="in" units="second" />
<variable cmeta:id="P_C2.kc" name="kc" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="P_C2.kc_" name="kc_" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="P_C2.P_O1" name="P_O1" public_interface="in" units="dimensionless" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>P_C2</ci>
</apply>
<apply>
<minus />
<apply>
<times />
<ci>kc</ci>
<ci>P_O1</ci>
</apply>
<apply>
<times />
<ci>kc_</ci>
<ci>P_C2</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="P_O_slow" cmeta:id="P_O_slow">
<variable cmeta:id="P_O_slow.P_O_slow" name="P_O_slow" public_interface="out" units="micromolar" />
<variable cmeta:id="P_O_slow.w" name="w" units="micromolar" />
<variable cmeta:id="P_O_slow.w_init" name="w_init" units="micromolar" />
<variable cmeta:id="P_O_slow.w_infinity_Cai" name="w_infinity_Cai" units="dimensionless" />
<variable cmeta:id="P_O_slow.tau_Cai" name="tau_Cai" units="dimensionless" />
<variable cmeta:id="P_O_slow.Ka" name="Ka" units="micromolar_4" />
<variable cmeta:id="P_O_slow.Kb" name="Kb" units="micromolar_3" />
<variable cmeta:id="P_O_slow.Kc" name="Kc" units="dimensionless" />
<variable cmeta:id="P_O_slow.ka" name="ka" public_interface="in" units="fifth_order_rate_constant" />
<variable cmeta:id="P_O_slow.kb" name="kb" public_interface="in" units="forth_order_rate_constant" />
<variable cmeta:id="P_O_slow.ka_" name="ka_" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="P_O_slow.kb_" name="kb_" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="P_O_slow.kc" name="kc" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="P_O_slow.kc_" name="kc_" public_interface="in" units="first_order_rate_constant" />
<variable cmeta:id="P_O_slow.Cai" name="Cai" public_interface="in" units="micromolar" />
<variable cmeta:id="P_O_slow.P_C2" name="P_C2" public_interface="in" units="micromolar" />
<variable cmeta:id="P_O_slow.time" name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="P_O_slow_calculation">
<eq />
<ci>P_O_slow</ci>
<apply>
<divide />
<apply>
<times />
<ci>w</ci>
<apply>
<plus />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.0</cn>
<apply>
<power />
<apply>
<divide />
<ci>Cai</ci>
<ci>Kb</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3.0</cn>
</apply>
</apply>
</apply>
<apply>
<plus />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.0</cn>
<apply>
<power />
<apply>
<divide />
<ci>Ka</ci>
<ci>Cai</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4.0</cn>
</apply>
<apply>
<power />
<apply>
<divide />
<ci>Cai</ci>
<ci>Kb</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3.0</cn>
</apply>
</apply>
</apply>
</apply>
<apply id="w_init_calculation">
<eq />
<ci>w_init</ci>
<apply>
<minus />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.0</cn>
<ci>P_C2</ci>
</apply>
</apply>
<apply id="w_infinity_Cai_calculation">
<eq />
<ci>w_infinity_Cai</ci>
<apply>
<divide />
<apply>
<plus />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.0</cn>
<apply>
<power />
<apply>
<divide />
<ci>Ka</ci>
<ci>Cai</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4.0</cn>
</apply>
<apply>
<power />
<apply>
<divide />
<ci>Cai</ci>
<ci>Kb</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3.0</cn>
</apply>
</apply>
<apply>
<plus />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.0</cn>
<apply>
<divide />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.0</cn>
<ci>Kc</ci>
</apply>
<apply>
<power />
<apply>
<divide />
<ci>Ka</ci>
<ci>Cai</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4.0</cn>
</apply>
<apply>
<power />
<apply>
<divide />
<ci>Cai</ci>
<ci>Kb</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3.0</cn>
</apply>
</apply>
</apply>
</apply>
<apply id="tau_Cai_calculation">
<eq />
<ci>tau_Cai</ci>
<apply>
<divide />
<ci>w_infinity_Cai</ci>
<ci>kc_</ci>
</apply>
</apply>
<apply id="Ka_calculation">
<eq />
<ci>Ka</ci>
<apply>
<divide />
<ci>ka_</ci>
<ci>ka</ci>
</apply>
</apply>
<apply id="Kb_calculation">
<eq />
<ci>Kb</ci>
<apply>
<divide />
<ci>kb_</ci>
<ci>kb</ci>
</apply>
</apply>
<apply id="Kc_calculation">
<eq />
<ci>Kc</ci>
<apply>
<divide />
<ci>kc_</ci>
<ci>kc</ci>
</apply>
</apply>
<apply id="w_diff_eq">
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>w</ci>
</apply>
<apply>
<divide />
<apply>
<minus />
<apply>
<minus />
<ci>w</ci>
<apply>
<times />
<ci>w_infinity_Cai</ci>
<ci>Cai</ci>
</apply>
</apply>
</apply>
<apply>
<times />
<ci>tau_Cai</ci>
<ci>Cai</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Cai" cmeta:id="Cai">
<variable cmeta:id="Cai.Cai" name="Cai" public_interface="out" units="micromolar" />
<variable cmeta:id="Cai.fi" initial_value="0.01" name="fi" units="dimensionless" />
<variable cmeta:id="Cai.v1" initial_value="40.0" name="v1" units="first_order_rate_constant" />
<variable cmeta:id="Cai.v2" initial_value="0.5" name="v2" units="first_order_rate_constant" />
<variable cmeta:id="Cai.v3" initial_value="1000.0" name="v3" units="second_order_rate_constant" />
<variable cmeta:id="Cai.K3" initial_value="0.30" name="K3" units="micromolar" />
<variable cmeta:id="Cai.Cas" name="Cas" units="micromolar" />
<variable cmeta:id="Cai.Co" initial_value="10.0" name="Co" units="micromolar" />
<variable cmeta:id="Cai.c1" initial_value="0.15" name="c1" units="dimensionless" />
<variable cmeta:id="Cai.P_O_slow" name="P_O_slow" public_interface="in" units="micromolar" />
<variable cmeta:id="Cai.time" name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="dCai_dt">
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>Cai</ci>
</apply>
<apply>
<times />
<ci>fi</ci>
<apply>
<minus />
<apply>
<times />
<apply>
<plus />
<apply>
<times />
<ci>v1</ci>
<ci>P_O_slow</ci>
</apply>
<ci>v2</ci>
</apply>
<apply>
<minus />
<ci>Cas</ci>
<ci>Cai</ci>
</apply>
</apply>
<apply>
<times />
<ci>v3</ci>
<apply>
<divide />
<apply>
<power />
<ci>Cai</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2.0</cn>
</apply>
<apply>
<plus />
<apply>
<power />
<ci>Cai</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2.0</cn>
</apply>
<apply>
<power />
<ci>K3</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2.0</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="Cas_calculation">
<eq />
<ci>Cas</ci>
<apply>
<divide />
<apply>
<minus />
<ci>Co</ci>
<ci>Cai</ci>
</apply>
<ci>c1</ci>
</apply>
</apply>
</math>
</component>
<component name="constants">
<variable cmeta:id="constants.ka" initial_value="1500.0" name="ka" public_interface="out" units="fifth_order_rate_constant" />
<variable cmeta:id="constants.kb" initial_value="1500.0" name="kb" public_interface="out" units="forth_order_rate_constant" />
<variable cmeta:id="constants.ka_" initial_value="28.8" name="ka_" public_interface="out" units="first_order_rate_constant" />
<variable cmeta:id="constants.kb_" initial_value="385.9" name="kb_" public_interface="out" units="first_order_rate_constant" />
<variable cmeta:id="constants.kc" initial_value="1.75" name="kc" public_interface="out" units="first_order_rate_constant" />
<variable cmeta:id="constants.kc_" initial_value="0.1" name="kc_" public_interface="out" units="first_order_rate_constant" />
<variable cmeta:id="constants.n" initial_value="4" name="n" public_interface="out" units="micromolar" />
<variable cmeta:id="constants.m" initial_value="3" name="m" public_interface="out" units="micromolar" />
</component>
<connection>
<map_components component_1="P_O1" component_2="P_C2" />
<map_variables variable_1="P_O1" variable_2="P_O1" />
</connection>
<connection>
<map_components component_1="P_C2" component_2="P_O1" />
<map_variables variable_1="P_C2" variable_2="P_C2" />
</connection>
<connection>
<map_components component_1="constants" component_2="P_C1" />
<map_variables variable_1="ka" variable_2="ka" />
<map_variables variable_1="n" variable_2="n" />
<map_variables variable_1="ka_" variable_2="ka_" />
</connection>
<connection>
<map_components component_1="constants" component_2="P_O2" />
<map_variables variable_1="kb_" variable_2="kb_" />
<map_variables variable_1="kb" variable_2="kb" />
<map_variables variable_1="m" variable_2="m" />
</connection>
<connection>
<map_components component_1="Cai" component_2="P_O1" />
<map_variables variable_1="Cai" variable_2="Cai" />
</connection>
<connection>
<map_components component_1="constants" component_2="P_O1" />
<map_variables variable_1="ka" variable_2="ka" />
<map_variables variable_1="kb_" variable_2="kb_" />
<map_variables variable_1="kc_" variable_2="kc_" />
<map_variables variable_1="kc" variable_2="kc" />
<map_variables variable_1="n" variable_2="n" />
<map_variables variable_1="ka_" variable_2="ka_" />
<map_variables variable_1="kb" variable_2="kb" />
<map_variables variable_1="m" variable_2="m" />
</connection>
<connection>
<map_components component_1="environment" component_2="P_O1" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="environment" component_2="P_C1" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="P_O1" component_2="P_O2" />
<map_variables variable_1="P_O1" variable_2="P_O1" />
</connection>
<connection>
<map_components component_1="Cai" component_2="P_O_slow" />
<map_variables variable_1="Cai" variable_2="Cai" />
</connection>
<connection>
<map_components component_1="Cai" component_2="P_C1" />
<map_variables variable_1="Cai" variable_2="Cai" />
</connection>
<connection>
<map_components component_1="environment" component_2="P_O_slow" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="P_C1" component_2="P_O1" />
<map_variables variable_1="P_C1" variable_2="P_C1" />
</connection>
<connection>
<map_components component_1="P_O_slow" component_2="Cai" />
<map_variables variable_1="P_O_slow" variable_2="P_O_slow" />
</connection>
<connection>
<map_components component_1="P_O1" component_2="P_C1" />
<map_variables variable_1="P_O1" variable_2="P_O1" />
</connection>
<connection>
<map_components component_1="environment" component_2="Cai" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="constants" component_2="P_C2" />
<map_variables variable_1="kc_" variable_2="kc_" />
<map_variables variable_1="kc" variable_2="kc" />
</connection>
<connection>
<map_components component_1="P_O2" component_2="P_O1" />
<map_variables variable_1="P_O2" variable_2="P_O2" />
</connection>
<connection>
<map_components component_1="environment" component_2="P_O2" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="Cai" component_2="P_O2" />
<map_variables variable_1="Cai" variable_2="Cai" />
</connection>
<connection>
<map_components component_1="environment" component_2="P_C2" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="P_C2" component_2="P_O_slow" />
<map_variables variable_1="P_C2" variable_2="P_C2" />
</connection>
<connection>
<map_components component_1="constants" component_2="P_O_slow" />
<map_variables variable_1="ka" variable_2="ka" />
<map_variables variable_1="kb_" variable_2="kb_" />
<map_variables variable_1="kc_" variable_2="kc_" />
<map_variables variable_1="kc" variable_2="kc" />
<map_variables variable_1="ka_" variable_2="ka_" />
<map_variables variable_1="kb" variable_2="kb" />
</connection>
<rdf:RDF xmlns:bqmodel="http://biomodels.net/model-qualifiers/" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:ro="http://www.obofoundry.org/ro/ro.owl#" xmlns:opb="http://bhi.washington.edu/OPB#">
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O1.kb">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#constants.kc_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O1.n">
<dcterms:description>ryanodine receptor calcium cooperativity parameter PC1 - PO1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_O_slow.Ka">
<dcterms:description>equilibrium constant of transition from PC1 to PO1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_C1.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O_slow.P_C2">
<dcterms:description>fraction of ryanodine receptors in state PC2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O_slow.Kb">
<dcterms:description>equilibrium constant of transition from PO1 to PO2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O_slow.ka">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#Cai.K3">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_5">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_0">
<ro:part_of>
<rdf:Description rdf:about="#entity_1">
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/fma/FMA:226050" />
</rdf:Description>
</ro:part_of>
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/chebi/CHEBI:29108" />
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>calcium dissociation constant of SERCA pump</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#constants.kc_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#P_O2.kb">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#P_C1.Cai">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_0">
<semsim:physicalPropertyOf rdf:resource="#entity_0" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>concentration of intracellular calcium</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_C2.P_C2">
<dcterms:description>fraction of ryanodine receptors in state PC2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cai.c1">
<dcterms:description>weighted volume fraction</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_O_slow.kb_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#entity_1">
<bqbiol:is rdf:resource="http://identifiers.org/fma/FMA:226050" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O1.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#P_O1.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#keizer_model_1996" semsim:modelName="keizer_levine_1996_version01" bqmodel:isDescribedBy="8968617">
<semsim:unknown>Keizer and Levine's 1996 model of a gating scheme for ryanodine
receptors.</semsim:unknown>
<semsim:modelName>keizer_levine_1996</semsim:modelName>
<semsim:unknown>Cardiac Myocyte</semsim:unknown>
</rdf:Description>
<rdf:Description rdf:about="#Cai.Cas">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_6">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_2">
<ro:part_of>
<rdf:Description rdf:about="#entity_3">
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/fma/FMA:62390" />
</rdf:Description>
</ro:part_of>
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/chebi/CHEBI:29108" />
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>concentration of calcium in the store</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_C2.kc_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O1.m">
<dcterms:description>ryanodine receptor calcium cooperativity parameter PO1 - PO2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#constants.m">
<dcterms:description>ryanodine receptor calcium cooperativity parameter PO1 - PO2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O_slow.w_init">
<dcterms:description>initial fraction of ryanodine receptor channels not in state PC2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_C1.ka">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#P_C2.kc">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#P_O1.ka_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_C2.P_O1">
<dcterms:description>fraction of ryanodine receptors in state PO1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cai.fi">
<dcterms:description>calcium buffer factor in cytoplasm</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O_slow.Ka">
<dcterms:description>equilibrium constant of transition from PC1 to PO1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O1.ka">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#P_O_slow.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#Cai.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#P_O2.m">
<dcterms:description>ryanodine receptor calcium cooperativity parameter PO1 - PO2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#constants.kb">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#Cai.Co">
<bqbiol:isPropertyOf>
<rdf:Description rdf:about="keizer_levine_1996.cellml#entity_4">
<bqbiol:is rdf:resource="https://identifiers.org/chebi/CHEBI:29108" />
</rdf:Description>
</bqbiol:isPropertyOf>
<dcterms:description>total calcium concentration in cell</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#constants.kb_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O_slow.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#P_O1.P_O2">
<dcterms:description>fraction of ryanodine receptors in state PO2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_C1.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O2.m">
<dcterms:description>ryanodine receptor calcium cooperativity parameter PO1 - PO2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#environment.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#P_O_slow.Kc">
<dcterms:description>equilibrium constant of transition from PO1 to PC2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_O2.Cai">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_2">
<semsim:physicalPropertyOf rdf:resource="#entity_0" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>concentration of intracellular calcium</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_C1.P_O1">
<dcterms:description>fraction of ryanodine receptors in state PO1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_O_slow.kb">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#constants.n">
<dcterms:description>ryanodine receptor calcium cooperativity parameter PC1 - PO1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_O1.P_C2">
<dcterms:description>fraction of ryanodine receptors in state PC2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_C1.n">
<dcterms:description>ryanodine receptor calcium cooperativity parameter PC1 - PO1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O_slow.kc_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_C1.ka_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#Cai.v2">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
<dcterms:description>maximal rate of store leak</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#Cai.Cai">
<bqbiol:isPropertyOf>
<rdf:Description rdf:about="keizer_levine_1996.cellml#entity_0">
<bqbiol:is rdf:resource="https://identifiers.org/chebi/CHEBI:29108" />
</rdf:Description>
</bqbiol:isPropertyOf>
<dcterms:description>concentration of intracellular calcium</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_C1.n">
<dcterms:description>ryanodine receptor calcium cooperativity parameter PC1 - PO1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cai.Cai">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_4">
<semsim:physicalPropertyOf rdf:resource="#entity_0" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>concentration of intracellular calcium</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_O_slow.P_C2">
<dcterms:description>fraction of ryanodine receptors in state PC2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#constants.kc">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#P_O_slow.kc_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#P_O1.P_O1">
<dcterms:description>fraction of ryanodine receptors in state PO1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O1.P_O1">
<dcterms:description>fraction of ryanodine receptors in state PO1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O_slow.Cai">
<bqbiol:isPropertyOf rdf:resource="keizer_levine_1996.cellml#entity_0" />
<dcterms:description>concentration of intracellular calcium</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O2.kb_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#P_O_slow.Kb">
<dcterms:description>equilibrium constant of transition from PO1 to PO2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_O_slow.ka">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#P_C2.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#constants.m">
<dcterms:description>ryanodine receptor calcium cooperativity parameter PO1 - PO2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_O1.kb_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_C2.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O1.P_C1">
<dcterms:description>fraction of ryanodine receptors in state PC1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_O1.P_C1">
<dcterms:description>fraction of ryanodine receptors in state PC1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O1.ka_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_C2.kc_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O_slow.P_O_slow">
<dcterms:description>open probability of ryanodine receptor channels in slow timescale</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O2.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#P_C1.P_C1">
<dcterms:description>fraction of ryanodine receptors in state PC1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#Cai.v3">
<dcterms:description>maximal rate of SERCA pump</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_C1.P_C1">
<dcterms:description>fraction of ryanodine receptors in state PC1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_O2.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#P_O1.n">
<dcterms:description>ryanodine receptor calcium cooperativity parameter PC1 - PO1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_O_slow.w_infinity_Cai">
<dcterms:description>steady state fraction of ryanodine receptor channels not in state PC2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O1.P_O2">
<dcterms:description>fraction of ryanodine receptors in state PO2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#constants.ka_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O2.kb">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#P_O1.kb">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_C1.P_O1">
<dcterms:description>fraction of ryanodine receptors in state PO1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_O2.P_O2">
<dcterms:description>fraction of ryanodine receptors in state PO2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#Cai.K3">
<bqbiol:isPropertyOf rdf:resource="keizer_levine_1996.cellml#entity_0" />
<dcterms:description>calcium dissociation constant of SERCA pump</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O1.P_C2">
<dcterms:description>fraction of ryanodine receptors in state PC2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#Cai.Cas">
<bqbiol:isPropertyOf>
<rdf:Description rdf:about="keizer_levine_1996.cellml#entity_2">
<bqbiol:is rdf:resource="https://identifiers.org/chebi/CHEBI:29108" />
</rdf:Description>
</bqbiol:isPropertyOf>
<dcterms:description>concentration of calcium in the store</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_C2.kc">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#P_O_slow.P_O_slow">
<dcterms:description>open probability of ryanodine receptor channels in slow timescale</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#constants.ka_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O_slow.kb_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#P_C2.P_C2">
<dcterms:description>fraction of ryanodine receptors in state PC2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#constants.kc">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#P_O2.kb_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#entity_5">
<bqbiol:is rdf:resource="http://identifiers.org/fma/FMA:67196" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#constants.ka">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#P_O_slow.kc">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#P_O_slow.Cai">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_3">
<semsim:physicalPropertyOf rdf:resource="#entity_0" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>concentration of intracellular calcium</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_O1.kc">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#Cai.P_O_slow">
<dcterms:description>open probability of ryanodine receptor channels in slow timescale</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cai.v3">
<dcterms:description>maximal rate of SERCA pump</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_O2.P_O1">
<dcterms:description>fraction of ryanodine receptors in state PO1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_O1.kc_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O_slow.w_infinity_Cai">
<dcterms:description>steady state fraction of ryanodine receptor channels not in state PC2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O1.kb_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O2.P_O1">
<dcterms:description>fraction of ryanodine receptors in state PO1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_C2.P_O1">
<dcterms:description>fraction of ryanodine receptors in state PO1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#Cai.v1">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
<dcterms:description>ryanodine receptor rate constant</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O1.Cai">
<bqbiol:isPropertyOf rdf:resource="keizer_levine_1996.cellml#entity_0" />
<dcterms:description>concentration of intracellular calcium</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#environment.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#Cai.Co">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_7">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_4">
<ro:part_of>
<rdf:Description rdf:about="#entity_5">
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/fma/FMA:67196" />
</rdf:Description>
</ro:part_of>
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/chebi/CHEBI:29108" />
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>total calcium concentration in cell</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#constants.kb">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O2.Cai">
<bqbiol:isPropertyOf rdf:resource="keizer_levine_1996.cellml#entity_0" />
<dcterms:description>concentration of intracellular calcium</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#keizer_model_1996" bqmodel:isDescribedBy="8968617" />
<rdf:Description rdf:about="#Cai.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#constants.n">
<dcterms:description>ryanodine receptor calcium cooperativity parameter PC1 - PO1</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cai.v2">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
<dcterms:description>maximal rate of store leak</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_O_slow.w_init">
<dcterms:description>initial fraction of ryanodine receptor channels not in state PC2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_C1.ka_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O2.P_O2">
<dcterms:description>fraction of ryanodine receptors in state PO2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O_slow.kc">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#constants.kb_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O_slow.ka_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#P_O1.Cai">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_1">
<semsim:physicalPropertyOf rdf:resource="#entity_0" />
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>concentration of intracellular calcium</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_O_slow.ka_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O1.kc">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#P_O1.m">
<dcterms:description>ryanodine receptor calcium cooperativity parameter PO1 - PO2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_C1.Cai">
<bqbiol:isPropertyOf rdf:resource="keizer_levine_1996.cellml#entity_0" />
<dcterms:description>concentration of intracellular calcium</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#Cai.c1">
<dcterms:description>weighted volume fraction</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#entity_3">
<bqbiol:is rdf:resource="http://identifiers.org/fma/FMA:62390" />
</rdf:Description>
<rdf:Description rdf:about="#constants.ka">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="#P_O_slow.w">
<dcterms:description>fraction of ryanodine receptor channels not in state PC2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cai.v1">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
<dcterms:description>ryanodine receptor rate constant</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_O1.ka">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#Cai.fi">
<dcterms:description>calcium buffer factor in cytoplasm</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cai.P_O_slow">
<dcterms:description>open probability of ryanodine receptor channels in slow timescale</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O1.kc_">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O_slow.Kc">
<dcterms:description>equilibrium constant of transition from PO1 to PC2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O_slow.w">
<dcterms:description>fraction of ryanodine receptor channels not in state PC2</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#P_C1.ka">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
<rdf:Description rdf:about="keizer_levine_1996.cellml#P_O_slow.kb">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01296" />
</rdf:Description>
</rdf:RDF>
</model>
