- Author:
- AnandR <a.rampadarath@auckland.ac.nz>
- Date:
- 2019-08-23 13:49:47+12:00
- Desc:
- CUrated models with annotation
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/556/rawfile/dca2baff06b50e43e313bf0a3eb0ae0c2c275698/niederer_hunter_smith_2006.cellml
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<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<section id="sec_status">
<title>Model Status</title>
<para>This model is known to run in OpenCell and COR to reproduce the output shown in the publication. The units have been checked and they are consistent.</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>Abstract: The determinants of relaxation in cardiac muscle are poorly understood, yet compromised relaxation accompanies various pathologies and impaired pump function. In this study, we develop a model of active contraction to elucidate the relative importance of the [Ca2+]i transient magnitude, the unbinding of Ca2+ from troponin C (TnC), and the length-dependence of tension and Ca2+ sensitivity on relaxation. Using the framework proposed by one of our researchers, we extensively reviewed experimental literature, to quantitatively characterize the binding of Ca2+ to TnC, the kinetics of tropomyosin, the availability of binding sites, and the kinetics of crossbridge binding after perturbations in sarcomere length. Model parameters were determined from multiple experimental results and modalities (skinned and intact preparations) and model results were validated against data from length step, caged Ca2+, isometric twitches, and the half-time to relaxation with increasing sarcomere length experiments. A factorial analysis found that the [Ca2+]i transient and the unbinding of Ca2+ from TnC were the primary determinants of relaxation, with a fivefold greater effect than that of length-dependent maximum tension and twice the effect of tension-dependent binding of Ca2+ to TnC and length-dependent Ca2+ sensitivity. The affects of the [Ca2+]i transient and the unbinding rate of Ca2+ from TnC were tightly coupled with the effect of increasing either factor, depending on the reference [Ca2+]i transient and unbinding rate.</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="niederer_2006.png" />
</imageobject>
</mediaobject>
<caption>Schematic diagram depicting the relationships of the active contraction framework proposed by Hunter et al. (11). The model is driven by SL and sarcomere velocity, and intracellular [Ca2+]i. Inputs are in bold, algebraic length dependencies are in italics, processes described by differential equations are standard font.</caption>
</informalfigure>
<para>The original publication reference is cited below:</para>
<para>
A Quantitative Analysis of Cardiac Myocyte Relaxation: A Simulation Study, Steven Niederer, Peter Hunter, Nicholas Smith, 2006
<emphasis>Biophysical Journal</emphasis>
, 90 1697-1722
<ulink url="http://www.ncbi.nlm.nih.gov/pubmed/16339881?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum">PubMed ID: 16339881</ulink>
</para>
</sect1>
</article>
</documentation>
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<times />
<ci>alpha_0</ci>
<apply>
<power />
<apply>
<divide />
<ci>Ca_b</ci>
<ci>Ca_TRPN_50</ci>
</apply>
<ci>n_Hill</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<ci>beta_Tm</ci>
<apply>
<plus />
<ci>alpha_r1</ci>
<apply>
<divide />
<apply>
<times />
<ci>alpha_r2</ci>
<apply>
<power />
<ci>z</ci>
<apply>
<minus />
<ci>n_Rel</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
<apply>
<plus />
<apply>
<power />
<ci>z</ci>
<ci>n_Rel</ci>
</apply>
<apply>
<power />
<ci>K_z</ci>
<ci>n_Rel</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>z</ci>
</apply>
<apply>
<minus />
<apply>
<times />
<ci>alpha_Tm</ci>
<apply>
<minus />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>z</ci>
</apply>
</apply>
<apply>
<times />
<ci>beta_Tm</ci>
<ci>z</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="troponin" cmeta:id="id_00008">
<variable cmeta:id="troponin.J_TRPN" name="J_TRPN" public_interface="out" units="mM_per_ms" />
<variable cmeta:id="troponin.Ca_TRPN_Max" initial_value="70e-3" name="Ca_TRPN_Max" public_interface="out" units="mM" />
<variable cmeta:id="troponin.TRPN" name="TRPN" public_interface="in" units="mM" />
<variable cmeta:id="troponin.Ca_i" name="Ca_i" public_interface="in" units="mM" />
<variable cmeta:id="troponin.k_off" name="k_off" units="per_ms" />
<variable cmeta:id="troponin.k_on" initial_value="100" name="k_on" public_interface="out" units="per_mM_per_ms" />
<variable cmeta:id="troponin.k_Ref_off" initial_value="0.2" name="k_Ref_off" public_interface="out" units="per_ms" />
<variable cmeta:id="troponin.gamma_trpn" initial_value="2" name="gamma_trpn" public_interface="out" units="dimensionless" />
<variable cmeta:id="troponin.Tension" name="Tension" public_interface="in" units="N_per_mm2" />
<variable cmeta:id="troponin.T_ref" name="T_ref" public_interface="in" units="N_per_mm2" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>k_off</ci>
<piecewise>
<piece>
<apply>
<times />
<ci>k_Ref_off</ci>
<apply>
<minus />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<divide />
<ci>Tension</ci>
<apply>
<times />
<ci>gamma_trpn</ci>
<ci>T_ref</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<gt />
<apply>
<minus />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<divide />
<ci>Tension</ci>
<apply>
<times />
<ci>gamma_trpn</ci>
<ci>T_ref</ci>
</apply>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.1</cn>
</apply>
</piece>
<otherwise>
<apply>
<times />
<ci>k_Ref_off</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.1</cn>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq />
<ci>J_TRPN</ci>
<apply>
<minus />
<apply>
<times />
<apply>
<minus />
<ci>Ca_TRPN_Max</ci>
<ci>TRPN</ci>
</apply>
<ci>k_off</ci>
</apply>
<apply>
<times />
<ci>Ca_i</ci>
<ci>TRPN</ci>
<ci>k_on</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Myofilaments" cmeta:id="id_00009">
<variable cmeta:id="Myofilaments.time" name="time" public_interface="in" units="ms" />
<variable cmeta:id="Myofilaments.lambda" name="lambda" public_interface="out" units="dimensionless" />
<variable cmeta:id="Myofilaments.ExtensionRatio" name="ExtensionRatio" public_interface="out" units="dimensionless" />
<variable cmeta:id="Myofilaments.dExtensionRatiodt" name="dExtensionRatiodt" public_interface="out" units="per_ms" />
<variable cmeta:id="Myofilaments.lambda_prev" name="lambda_prev" public_interface="out" units="dimensionless" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>ExtensionRatio</ci>
<piecewise>
<piece>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<gt />
<ci>time</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="ms">1000</cn>
</apply>
</piece>
<otherwise>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
</otherwise>
</piecewise>
</apply>
<apply>
<eq />
<ci>lambda_prev</ci>
<ci>ExtensionRatio</ci>
</apply>
<apply>
<eq />
<ci>dExtensionRatiodt</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_ms">0</cn>
</apply>
<apply>
<eq />
<ci>lambda</ci>
<piecewise>
<piece>
<ci>ExtensionRatio</ci>
<apply>
<and />
<apply>
<gt />
<ci>ExtensionRatio</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.8</cn>
</apply>
<apply>
<leq />
<ci>ExtensionRatio</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.15</cn>
</apply>
</apply>
</piece>
<piece>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.15</cn>
<apply>
<gt />
<ci>ExtensionRatio</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.15</cn>
</apply>
</piece>
<otherwise>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.8</cn>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<component name="filament_overlap" cmeta:id="id_00010">
<variable cmeta:id="filament_overlap.lambda" name="lambda" public_interface="in" units="dimensionless" />
<variable cmeta:id="filament_overlap.overlap" name="overlap" public_interface="out" units="dimensionless" />
<variable cmeta:id="filament_overlap.beta_0" initial_value="4.9" name="beta_0" public_interface="out" units="dimensionless" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>overlap</ci>
<apply>
<plus />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<times />
<ci>beta_0</ci>
<apply>
<minus />
<ci>lambda</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="length_independent_tension">
<variable cmeta:id="length_independent_tension.T_ref" initial_value="56.2" name="T_ref" public_interface="out" units="N_per_mm2" />
<variable cmeta:id="length_independent_tension.T_Base" name="T_Base" public_interface="out" units="N_per_mm2" />
<variable cmeta:id="length_independent_tension.z" name="z" public_interface="in" units="dimensionless" />
<variable cmeta:id="length_independent_tension.z_max" name="z_max" public_interface="in" units="dimensionless" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>T_Base</ci>
<apply>
<divide />
<apply>
<times />
<ci>T_ref</ci>
<ci>z</ci>
</apply>
<ci>z_max</ci>
</apply>
</apply>
</math>
</component>
<component name="isometric_tension">
<variable cmeta:id="isometric_tension_T0" name="T_0" public_interface="out" units="N_per_mm2" />
<variable cmeta:id="isometric_tension.T_Base" name="T_Base" public_interface="in" units="N_per_mm2" />
<variable cmeta:id="isometric_tension.overlap" name="overlap" public_interface="in" units="dimensionless" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>T_0</ci>
<apply>
<times />
<ci>T_Base</ci>
<ci>overlap</ci>
</apply>
</apply>
</math>
</component>
<component name="Cross_Bridges">
<variable cmeta:id="Cross_Bridges.time" name="time" public_interface="in" units="ms" />
<variable cmeta:id="Cross_Bridges.dExtensionRatiodt" name="dExtensionRatiodt" public_interface="in" units="per_ms" />
<variable cmeta:id="Cross_Bridges.Q" name="Q" units="dimensionless" />
<variable cmeta:id="Cross_Bridges.a" initial_value="0.35" name="a" units="dimensionless" />
<variable cmeta:id="Cross_Bridges.Q_1" initial_value="0" name="Q_1" units="dimensionless" />
<variable cmeta:id="Cross_Bridges.Q_2" initial_value="0" name="Q_2" units="dimensionless" />
<variable cmeta:id="Cross_Bridges.Q_3" initial_value="0" name="Q_3" units="dimensionless" />
<variable cmeta:id="Cross_Bridges.A_1" initial_value="-29" name="A_1" units="dimensionless" />
<variable cmeta:id="Cross_Bridges.A_2" initial_value="138" name="A_2" units="dimensionless" />
<variable cmeta:id="Cross_Bridges.A_3" initial_value="129" name="A_3" units="dimensionless" />
<variable cmeta:id="Cross_Bridges.alpha_1" initial_value="0.03" name="alpha_1" units="per_ms" />
<variable cmeta:id="Cross_Bridges.alpha_2" initial_value="0.13" name="alpha_2" units="per_ms" />
<variable cmeta:id="Cross_Bridges.alpha_3" initial_value="0.625" name="alpha_3" units="per_ms" />
<variable cmeta:id="Cross_Bridges.T_0" name="T_0" public_interface="in" units="N_per_mm2" />
<variable cmeta:id="Cross_Bridges_Tension" name="Tension" public_interface="out" units="N_per_mm2" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq />
<ci>Q</ci>
<apply>
<plus />
<ci>Q_1</ci>
<ci>Q_2</ci>
<ci>Q_3</ci>
</apply>
</apply>
<apply>
<eq />
<ci>Tension</ci>
<piecewise>
<piece>
<apply>
<divide />
<apply>
<times />
<ci>T_0</ci>
<apply>
<plus />
<apply>
<times />
<ci>a</ci>
<ci>Q</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
</apply>
</apply>
<apply>
<minus />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>Q</ci>
</apply>
</apply>
<apply>
<lt />
<ci>Q</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0</cn>
</apply>
</piece>
<otherwise>
<apply>
<divide />
<apply>
<times />
<ci>T_0</ci>
<apply>
<plus />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<times />
<apply>
<plus />
<ci>a</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
<ci>Q</ci>
</apply>
</apply>
</apply>
<apply>
<plus />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>Q</ci>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>Q_1</ci>
</apply>
<apply>
<minus />
<apply>
<times />
<ci>A_1</ci>
<ci>dExtensionRatiodt</ci>
</apply>
<apply>
<times />
<ci>alpha_1</ci>
<ci>Q_1</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>Q_2</ci>
</apply>
<apply>
<minus />
<apply>
<times />
<ci>A_2</ci>
<ci>dExtensionRatiodt</ci>
</apply>
<apply>
<times />
<ci>alpha_2</ci>
<ci>Q_2</ci>
</apply>
</apply>
</apply>
<apply>
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>Q_3</ci>
</apply>
<apply>
<minus />
<apply>
<times />
<ci>A_3</ci>
<ci>dExtensionRatiodt</ci>
</apply>
<apply>
<times />
<ci>alpha_3</ci>
<ci>Q_3</ci>
</apply>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_1="tropomyosin" component_2="length_independent_tension" />
<map_variables variable_1="z" variable_2="z" />
<map_variables variable_1="z_max" variable_2="z_max" />
</connection>
<connection>
<map_components component_1="environment" component_2="Myofilaments" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="filament_overlap" component_2="tropomyosin" />
<map_variables variable_1="beta_0" variable_2="beta_0" />
</connection>
<connection>
<map_components component_1="Myofilaments" component_2="filament_overlap" />
<map_variables variable_1="lambda" variable_2="lambda" />
</connection>
<connection>
<map_components component_1="environment" component_2="Cross_Bridges" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="Myofilaments" component_2="Cross_Bridges" />
<map_variables variable_1="dExtensionRatiodt" variable_2="dExtensionRatiodt" />
</connection>
<connection>
<map_components component_1="length_independent_tension" component_2="troponin" />
<map_variables variable_1="T_ref" variable_2="T_ref" />
</connection>
<connection>
<map_components component_1="isometric_tension" component_2="Cross_Bridges" />
<map_variables variable_1="T_0" variable_2="T_0" />
</connection>
<connection>
<map_components component_1="length_independent_tension" component_2="isometric_tension" />
<map_variables variable_1="T_Base" variable_2="T_Base" />
</connection>
<connection>
<map_components component_1="Cross_Bridges" component_2="troponin" />
<map_variables variable_1="Tension" variable_2="Tension" />
</connection>
<connection>
<map_components component_1="intracellular_ion_concentrations" component_2="tropomyosin" />
<map_variables variable_1="Ca_b" variable_2="Ca_b" />
</connection>
<connection>
<map_components component_1="Myofilaments" component_2="tropomyosin" />
<map_variables variable_1="lambda" variable_2="lambda" />
</connection>
<connection>
<map_components component_1="troponin" component_2="tropomyosin" />
<map_variables variable_1="gamma_trpn" variable_2="gamma_trpn" />
<map_variables variable_1="Ca_TRPN_Max" variable_2="Ca_TRPN_Max" />
<map_variables variable_1="k_on" variable_2="k_on" />
<map_variables variable_1="k_Ref_off" variable_2="k_Ref_off" />
</connection>
<connection>
<map_components component_1="environment" component_2="intracellular_ion_concentrations" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="intracellular_ion_concentrations" component_2="troponin" />
<map_variables variable_1="Ca_i" variable_2="Ca_i" />
<map_variables variable_1="TRPN" variable_2="TRPN" />
</connection>
<connection>
<map_components component_1="environment" component_2="tropomyosin" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="troponin" component_2="intracellular_ion_concentrations" />
<map_variables variable_1="J_TRPN" variable_2="J_TRPN" />
<map_variables variable_1="Ca_TRPN_Max" variable_2="Ca_TRPN_Max" />
</connection>
<connection>
<map_components component_1="filament_overlap" component_2="isometric_tension" />
<map_variables variable_1="overlap" variable_2="overlap" />
</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="#troponin.k_on">
<dcterms:description>Rate of binding of Ca2+ to troponin C</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#id_00004">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_3">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_5" dcterms:description="">
<semsim:name>Ca2+ bound to troponin C</semsim:name>
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Maximum concentration of Ca2+ that can bind to troponin C</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#intracellular_ion_concentrations.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#environment_time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.alpha_1">
<dcterms:description>Exponential function 1 for the fading memory model</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#length_independent_tension.z_max">
<dcterms:description>The fraction of actin sites available at full (Max) activation</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.A_3">
<dcterms:description>Weighting function 3 for the fading memory model</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#id_00012">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_5">
<semsim:physicalPropertyOf rdf:resource="#entity_5" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Maximum concentration of Ca2+ that can bind to troponin C</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#Myofilaments.time">
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#troponin.J_TRPN">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_9">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#process_0" dcterms:description="">
<semsim:hasSinkParticipant>
<rdf:Description rdf:about="#sink_1" semsim:hasMultiplier="1.0">
<semsim:hasPhysicalEntityReference>
<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="http://identifiers.org/chebi/CHEBI:29108" />
</rdf:Description>
</semsim:hasPhysicalEntityReference>
</rdf:Description>
</semsim:hasSinkParticipant>
<semsim:hasSinkParticipant>
<rdf:Description rdf:about="#sink_0" semsim:hasMultiplier="1.0">
<semsim:hasPhysicalEntityReference>
<rdf:Description rdf:about="#entity_4">
<ro:part_of>
<rdf:Description rdf:about="#entity_3">
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/fma/FMA:14067" />
</rdf:Description>
</ro:part_of>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/chebi/CHEBI:29108" />
</rdf:Description>
</semsim:hasPhysicalEntityReference>
</rdf:Description>
</semsim:hasSinkParticipant>
<semsim:hasSourceParticipant>
<rdf:Description rdf:about="#source_0" semsim:hasMultiplier="1.0">
<semsim:hasPhysicalEntityReference>
<rdf:Description rdf:about="#entity_6" dcterms:description="">
<semsim:name>Ca2+ bound to troponin C</semsim:name>
</rdf:Description>
</semsim:hasPhysicalEntityReference>
</rdf:Description>
</semsim:hasSourceParticipant>
<semsim:name>Dissociation of Ca2+ from Troponin C</semsim:name>
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00593" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Flux of Calcium bounded to Troponin C</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#troponin.Ca_i">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_12">
<semsim:physicalPropertyOf rdf:resource="#entity_0" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of free Ca(2+) in the sarcomare of a Caridac muscle cell.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.z_max">
<dcterms:description>The fraction of actin sites available at full (Max) activation</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#troponin.Ca_TRPN_Max">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_10">
<semsim:physicalPropertyOf rdf:resource="#entity_5" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Maximum concentration of Ca2+ that can bind to troponin C</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#intracellular_ion_concentrations_Ca_i">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_0">
<semsim:physicalPropertyOf rdf:resource="#entity_0" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of free Ca(2+) in the sarcomare of a Caridac muscle cell.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#id_00003">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_2">
<semsim:physicalPropertyOf rdf:resource="#entity_4" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of Ca(2+) in Cardiac Myocyte</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#length_independent_tension.z">
<dcterms:description>The fraction of actin sites available for crossbridge binding</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.alpha_2">
<dcterms:description>Exponential function 2 for the fading memory model</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#length_independent_tension.T_ref">
<dcterms:description>Maximum tension at resting SL.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#id_00011">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_7">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_2" dcterms:description="">
<ro:part_of rdf:resource="#entity_3" />
<semsim:name>Ca2+ bound to troponin C</semsim:name>
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of Ca2+ bound to TnC at half activation of Tension</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.T_0">
<dcterms:description>Isometric tension as a function of both arcomere length and
thin filament kinetics,</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges_Tension">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_14">
<semsim:physicalPropertyOf rdf:resource="#entity_3" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_01097" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Isometric tension produced by crossbridges in the cardiac muscle.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#id_00002">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_1">
<semsim:physicalPropertyOf rdf:resource="#entity_2" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of Ca2+ bound to troponin C</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#id_00014">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_6">
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Ca(2+) concentration for half activation of tension.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.alpha_3">
<dcterms:description>Exponential function 3 for the fading memory model</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#troponin.k_Ref_off">
<dcterms:description>Unbinding rate in the absence of tension</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.A_1">
<dcterms:description>Weighting function 1for the fading memory model</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#troponin.T_ref">
<dcterms:description>Maximum tension at resting SL.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.k_on">
<dcterms:description>Rate of binding of Ca2+ to troponin C</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#troponin.TRPN">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_11">
<semsim:physicalPropertyOf rdf:resource="#entity_4" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of Ca(2+) in Cardiac Myocyte</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#id_00005">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_4">
<semsim:physicalPropertyOf rdf:resource="#process_0" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00593" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Flux of Calcium bounded to Troponin C</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.k_Ref_off">
<dcterms:description>Unbinding rate in the absence of tension</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#id_00013">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_8">
<semsim:physicalPropertyOf rdf:resource="#entity_2" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of Ca2+ bound to troponin C</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#niederer_2006" semsim:modelName="niederer_hunter_smith_20061" bqmodel:isDescribedBy="16339881">
<semsim:modelName>niederer_hunter_smith_2006</semsim:modelName>
<semsim:modelName>niederer_2006</semsim:modelName>
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.a">
<dcterms:description>Measure of the curvature of the force-velocity relation.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.z">
<dcterms:description>The fraction of actin sites available for crossbridge binding</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.A_2">
<dcterms:description>Weighting function 2for the fading memory model</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#troponin.k_off">
<dcterms:description>Tension-dependent rate of unbinding of Ca2+ from Troponin C</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#troponin.Tension">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_13">
<semsim:physicalPropertyOf rdf:resource="#entity_3" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_01097" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Isometric tension produced by crossbridges in the cardiac muscle.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#isometric_tension_T0">
<dcterms:description>Isometric tension as a function of both arcomere length and
thin filament kinetics,</dcterms:description>
</rdf:Description>
</rdf:RDF>
</model>
