Cooperative Mechanisms in Cardiac Muscle |  PDF |
Catherine Lloyd (Bioengineering Institute, University of Auckland)
Table of Contents
In cardiac muscle, steady-state force-Ca2+ (F-Ca) relations exhibit more cooperativity than that predicted by the single Ca2+ binding site on troponin. The exact mechanisms underlying this high cooperativity are unknown. In their 1999 paper, J. Jeremy Rice, Raimond L. Winslow and William C. Hunter present five potential models for force generation in cardiac muscle (see Figure 1 below). These models were constructed by assuming different subsets of three possible cooperative mechanisms:
Cooperative mechanism 1 — is based on the theory that cross bridge formation between actin and myosin increases the affinity of troponin for Ca2+.
Cooperative mechanism 2 — assumes that the binding of a cross bridge increases the rate of formation of neighbouring cross bridges and that multiple cross bridges can actin activation even in the absence of Ca2+.
Cooperative mechanism 2 — simulates end-to-end interactions between adjacent troponin and tropomyosin.
Comparison of putative cooperative mechanisms in cardiac muscle: length dependence and dynamic responses J. Jeremy Rice, Raimond L. Winslow and William C. Hunter, 1999, American Journal of Physiology, 276, H1734-H1754. (Full text and PDF versions of the article are available for Journal Members on the American Journal of Physiology website.) PubMed ID: 10330260
All the models are similar in that they are structured around a functional unit of troponin, tropomyosin and actin. Tropomyosin can exist in four states, two permissive or two non-permissive (referring to whether or not the actin sites are available for binding to myosin and hence cross bridge formation). Depending on the model, one or more cross bridges exist, and these are either weakly-bound (non-force generating) or strongly bound (force generating).
The paper (cited below) tests the behaviours of the five models of force generation in cardiac myocytes. The first two models provide a baseline of performance for comparison. Models 3 to 5 are developed to incorporate more cooperative mechanisms. From the results of these simulations, which were compared to and consistent with experimental data, it is hypothesised that multiple mechanisms of cooperativity may coexist and contribute to the responses of cardiac muscle.
rice_model1_1999.xml — the raw XML.
rice_model1_1999.html — an HTML version for browsing online.
rice_model1_1999.pdf — a PDF version suitable for printing.
cellml_rice_model1_1999.tar.gz — a gzipped tarball with the XML and this documentation.
rice_model1_1999_maths.pdf — a PDF of the equations described in the model generated directly from the CellML description using the MathML Renderer.
rice_model2_1999.xml — the raw XML.
rice_model2_1999.html — an HTML version for browsing online.
rice_model2_1999.pdf — a PDF version suitable for printing.
cellml_rice_model2_1999.tar.gz — a gzipped tarball with the XML and this documentation.
rice_model2_1999_maths.pdf — a PDF of the equations described in the model generated directly from the CellML description using the MathML Renderer.
rice_model3_1999.xml — the raw XML.
rice_model3_1999.html — an HTML version for browsing online.
rice_model3_1999.pdf — a PDF version suitable for printing.
cellml_rice_model3_1999.tar.gz — a gzipped tarball with the XML and this documentation.
rice_model3_1999_maths.pdf — a PDF of the equations described in the model generated directly from the CellML description using the MathML Renderer.
rice_model4_1999.xml — the raw XML.
rice_model4_1999.html — an HTML version for browsing online.
rice_model4_1999.pdf — a PDF version suitable for printing.
cellml_rice_model4_1999.tar.gz — a gzipped tarball with the XML and this documentation.
rice_model4_1999_maths.pdf — a PDF of the equations described in the model generated directly from the CellML description using the MathML Renderer.
rice_model5_1999.xml — the raw XML.
rice_model5_1999.html — an HTML version for browsing online.
rice_model5_1999.pdf — a PDF version suitable for printing.
cellml_rice_model5_1999.tar.gz — a gzipped tarball with the XML and this documentation.
rice_model5_1999_maths.pdf — a PDF of the equations described in the model generated directly from the CellML description using the MathML Renderer.
