- Author:
- Dewan Sarwar <dsar941@UoA.auckland.ac.nz>
- Date:
- 2020-03-03 16:11:04+13:00
- Desc:
- minor typos in the protocol 13's rdf files
- Permanent Source URI:
- https://models.cellml.org/workspace/267/rawfile/1c91b119a0cc3f2842ec5cb1f878542e91df490f/niederer_hunter_smith_2006.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="niederer_hunter_smith_2006" cmeta:id="niederer_2006">
<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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<unit units="mM" />
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<rdf:Description rdf:about="#entity_0">
<ro:part_of>
<rdf:Description rdf:about="#entity_1">
<ro:part_of>
<rdf:Description rdf:about="#entity_2">
<semsim:hasPhysicalDefinition rdf:resource="http://purl.obolibrary.org/obo/FMA_14067" />
</rdf:Description>
</ro:part_of>
<semsim:hasPhysicalDefinition rdf:resource="http://purl.obolibrary.org/obo/FMA_66836" />
</rdf:Description>
</ro:part_of>
<semsim:hasPhysicalDefinition rdf:resource="http://purl.obolibrary.org/obo/CHEBI_29108" />
</rdf:Description>
</semsim:physicalPropertyOf>
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Intracellular calcium (2+) concentration</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.z_max">
<dcterms:description>the maximum fraction of available actin sites at a given sarcomere length</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#intracellular_ion_concentrations_Ca_i">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_5">
<semsim:physicalPropertyOf rdf:resource="#entity_0" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Intracellular calcium (2+) concentration</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Myofilaments.ExtensionRatio">
<dcterms:description>Sarcomere strain</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.alpha_2">
<dcterms:description>Exponential rate constant for process 2 of the crossbridge kinetics fading memory model</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.T_0">
<dcterms:description>The isometric tension at a given intracellular calcium ion concentration and sarcomere length</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges_Tension">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_2">
<semsim:physicalPropertyOf rdf:resource="#entity_2" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_01097" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Active tension of cardiac myocyte</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.Q_1">
<dcterms:description>Exponential process 1 of the crossbridge kinetics fading memory model</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.alpha_3">
<dcterms:description>Exponential rate constant for process 3 of the crossbridge kinetics fading memory model</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.gamma_trpn">
<dcterms:description>A measure of the effect of tension on the unbinding rate of calcium (2+) from troponin C</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.A_1">
<dcterms:description>Weighting coefficient for process 1 of the crossbridge kinetics fading memory model</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#intracellular_ion_concentrations.Ca_b">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_4">
<semsim:physicalPropertyOf>
<rdf:Description rdf:about="#entity_3">
<ro:part_of rdf:resource="#entity_1" />
<dcterms:description>Calcium (2+) ion bound to site II of troponin C</dcterms:description>
<semsim:name>Calcium (2+) 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 calcium (2+) bound to troponin C</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#troponin.T_ref">
<dcterms:description>Maximum tension at resting sarcomere length</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#filament_overlap.beta_0">
<dcterms:description>Scaling factor (slope) for the relationship between lambda and T_0</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.alpha_r1">
<dcterms:description>Slow relaxation rate parameter for computing z</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.k_on">
<dcterms:description>The binding rate of calcium (2+) to troponin C site II</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.k_Ref_off">
<dcterms:description>Rate of calcium (2+) unbinding from Troponin C in the absence of tension</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.Q_2">
<dcterms:description>Exponential process 2 of the crossbridge kinetics fading memory model</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#process_0">
<dcterms:description>In this model, the formation of troponin C comes from the dissociation of the calcium (2+) / troponin C complex</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#niederer_2006" semsim:modelName="niederer_hunter_smith_2006" bqmodel:isDescribedBy="16339881">
<semsim:modelName>niederer_2006</semsim:modelName>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.alpha_0">
<dcterms:description>The monoexponential activation rate seen in caged calcium (2+) experiments. Used to compute z.</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.z">
<dcterms:description>The fraction of actin sites available for crossbridge binding as determined by thin filament kinetics</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.A_2">
<dcterms:description>Weighting coefficient for process 2 of the crossbridge kinetics fading memory model</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#troponin.k_off">
<dcterms:description>The unbinding rate of calcium (2+) from troponin C site II</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.n_Rel">
<dcterms:description>Fast relaxation rate parameter for computing z</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#environment_time">
<dcterms:description>Temporal solution domain</dcterms:description>
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.Q_3">
<dcterms:description>Exponential process 3 of the crossbridge kinetics fading memory model</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.K_2">
<dcterms:description>Linearization term for computing z_max</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.alpha_Tm">
<dcterms:description>Intermediate term for first component of varaible z's ODE (equation 9 in reference paper)</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#length_independent_tension.z_max">
<dcterms:description>The fraction of actin sites available at full activation</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.time">
<dcterms:description>Temporal solution domain</dcterms:description>
<bqbiol:is rdf:resource="http://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.A_3">
<dcterms:description>Weighting coefficient for process 3 of the crossbridge kinetics fading memory model</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="http://www.cellml.org/cellml/1.0">
<dc:publisher>Auckland Bioengineering Institute</dc:publisher>
<cmeta:comment>
<rdf:Description rdf:about="rdf:#22da1e29-04c8-420d-936b-bd8b2e486104">
<dc:creator>
<rdf:Description rdf:about="rdf:#314dbed2-8642-4da9-80fd-945b5d1ec7ea">
<vCard:FN>James Lawson</vCard:FN>
</rdf:Description>
</dc:creator>
<rdf:value>This model can be simulated in COR and PCEnv and is able to reproduce the results published in Niederer et al.'s 2006 paper.</rdf:value>
</rdf:Description>
</cmeta:comment>
<dcterms:created rdf:resource="rdf:#47b74e5d-97ed-4aaa-a687-07fd8f195b42" dcterms:W3CDTF="2008-01-07T00:00:00+00:00" />
<dc:creator>
<rdf:Description rdf:about="rdf:#e137d61c-82dc-4189-b9f0-29b66171c2e1">
<vCard:ORG>
<rdf:Description rdf:about="rdf:#ef3cf40f-3b42-4ed0-993c-730bdf918afc">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>Auckland Bioengineering Institute</vCard:Orgunit>
</rdf:Description>
</vCard:ORG>
<vCard:EMAIL rdf:resource="rdf:#53e5d308-54da-4612-80cc-b8391fe05593" rdf:value="j.terkildsen@auckland.ac.nz" rdf:type="http://imc.org/vCard/3.0#internet" />
<vCard:N rdf:resource="rdf:#02fbf752-3e20-4809-818c-bd7725477072" vCard:Given="Jonna" vCard:Family="Terkildsen" vCard:Other="" />
</rdf:Description>
</dc:creator>
<cmeta:modification>
<rdf:Description rdf:about="rdf:#09f3904b-dd66-4a28-abac-7bb5cd351965">
<dcterms:modified rdf:resource="rdf:#a4cc9a49-f551-4ae0-8ce6-2c5513162628" dcterms:W3CDTF="2008-08-05T10:32:30+12:00" />
<rdf:value>added cmeta id to T_0 variable</rdf:value>
<cmeta:modifier>
<rdf:Description rdf:about="rdf:#7f8791df-4ef7-4dcc-963d-9a0480c65a43">
<vCard:N rdf:resource="rdf:#5558142b-a43a-435c-aa8d-7da64599a4cc" vCard:Given="James" vCard:Family="Lawson" vCard:Other="Richard" />
</rdf:Description>
</cmeta:modifier>
</rdf:Description>
</cmeta:modification>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.lambda">
<dcterms:description>Sarcomere strain?</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.z_p">
<dcterms:description>Point around which the non-linear component of equation 9 in the paper (solving for dz/dt) is linearized to maintain an explicit formulation for the model</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Myofilaments.lambda">
<dcterms:description>Sarcomere strain, constrained to values between 0.8 and 1.15</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.Ca_b">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_3">
<semsim:physicalPropertyOf rdf:resource="#entity_3" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_00340" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Concentration of calcium (2+) bound to troponin C</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.beta_0">
<dcterms:description>Scaling factor (slope) for the relationship between lambda and T_0</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="#length_independent_tension.T_ref">
<dcterms:description>Maximum tension at resting sarcomere length</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#isometric_tension.T_Base">
<dcterms:description>Isometric tension of cell</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Myofilaments.lambda_prev">
<dcterms:description>Mystery variable mathematically equal to sarcomere strain</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#filament_overlap.lambda">
<dcterms:description>Sarcomere strain?</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#filament_overlap.overlap">
<dcterms:description>Sarcomere overlap?</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.K_z">
<dcterms:description>Fast relaxation rate parameter for computing z</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.beta_1">
<dcterms:description>Scaling parameter for Ca_50 vs. lambda dependency</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#troponin.k_Ref_off">
<dcterms:description>Rate of calcium (2+) unbinding from Troponin C in the absence of tension</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.n_Hill">
<dcterms:description>Analogous to the Hill coefficient in the steady-state force-calcium (2+) curve (F-pCa) and provides a phenomenological rep- resentation of the high cooperativity, due to nearest-neighbor interactions between tropomyosin and/or crossbridges, seen in the activation of tension in cardiac muscle</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.K_1">
<dcterms:description>Linearization term for computing z_max</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.a">
<dcterms:description>Curve-shaping constant for relationship between relative sarcomere velocity and relative tension</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#tropomyosin.beta_Tm">
<dcterms:description>Intermediate term for second component of variable z's ODE (equation 9 in reference paper)</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#troponin.gamma_trpn">
<dcterms:description>A measure of the effect of tension on the unbinding rate of calcium (2+) from troponin C</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#length_independent_tension.T_Base">
<dcterms:description>Isometric tension of cell</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#troponin.Tension">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_1">
<semsim:physicalPropertyOf rdf:resource="#entity_2" />
<semsim:hasPhysicalDefinition rdf:resource="http://identifiers.org/opb/OPB_01097" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>Active tension of cardiac myocyte</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#Cross_Bridges.Q">
<dcterms:description>Sum of the three exponential processes in the crossbridge dynamics fading memory model</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#isometric_tension_T0">
<dcterms:description>The isometric tension at a given intracellular calcium ion concentration and sarcomere length</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#niederer_hunter_smith_2006">
<ro:modelOf rdf:resource="http://purl.obolibrary.org/obo/PR_P63316" />
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</rdf:RDF>
</model>
