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High tension in sarcomeres hinders myocardial relaxation: A computational study
Experiments have shown that the relaxation phase of cardiac sarcomeres during an isometric twitch is prolonged in muscles that reached a higher peak tension. However, the mechanism is not completely understood. We hypothesize that the binding of calcium to troponin is enhanced by the tension in the...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171862/ https://www.ncbi.nlm.nih.gov/pubmed/30286135 http://dx.doi.org/10.1371/journal.pone.0204642 |
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author | Dupuis, Lauren J. Lumens, Joost Arts, Theo Delhaas, Tammo |
author_facet | Dupuis, Lauren J. Lumens, Joost Arts, Theo Delhaas, Tammo |
author_sort | Dupuis, Lauren J. |
collection | PubMed |
description | Experiments have shown that the relaxation phase of cardiac sarcomeres during an isometric twitch is prolonged in muscles that reached a higher peak tension. However, the mechanism is not completely understood. We hypothesize that the binding of calcium to troponin is enhanced by the tension in the thin filament, thus contributing to the prolongation of contraction upon higher peak tension generation. To test this hypothesis, we developed a computational model of sarcomere mechanics that incorporates tension-dependence of calcium binding. The model was used to simulate isometric twitch experiments with time dependency in the form of a two-state cross-bridge cycle model and a transient intracellular calcium concentration. In the simulations, peak isometric twitch tension appeared to increase linearly by 51.1 KPa with sarcomere length from 1.9 μm to 2.2 μm. Experiments showed an increase of 47.3 KPa over the same range of sarcomere lengths. The duration of the twitch also increased with both sarcomere length and peak intracellular calcium concentration, likely to be induced by the inherently coupled increase of the peak tension in the thin filament. In the model simulations, the time to 50% relaxation (t(R50)) increased over the range of sarcomere lengths from 1.9 μm to 2.2 μm by 0.11s, comparable to the increased duration of 0.12s shown in experiments. Model simulated t(R50) increased by 0.12s over the range of peak intracellular calcium concentrations from 0.87 μM to 1.45 μM. Our simulation results suggest that the prolongation of contraction at higher tension is a result of the tighter binding of Ca(2+) to troponin in areas under higher tension, thus delaying the deactivation of the troponin. |
format | Online Article Text |
id | pubmed-6171862 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-61718622018-10-19 High tension in sarcomeres hinders myocardial relaxation: A computational study Dupuis, Lauren J. Lumens, Joost Arts, Theo Delhaas, Tammo PLoS One Research Article Experiments have shown that the relaxation phase of cardiac sarcomeres during an isometric twitch is prolonged in muscles that reached a higher peak tension. However, the mechanism is not completely understood. We hypothesize that the binding of calcium to troponin is enhanced by the tension in the thin filament, thus contributing to the prolongation of contraction upon higher peak tension generation. To test this hypothesis, we developed a computational model of sarcomere mechanics that incorporates tension-dependence of calcium binding. The model was used to simulate isometric twitch experiments with time dependency in the form of a two-state cross-bridge cycle model and a transient intracellular calcium concentration. In the simulations, peak isometric twitch tension appeared to increase linearly by 51.1 KPa with sarcomere length from 1.9 μm to 2.2 μm. Experiments showed an increase of 47.3 KPa over the same range of sarcomere lengths. The duration of the twitch also increased with both sarcomere length and peak intracellular calcium concentration, likely to be induced by the inherently coupled increase of the peak tension in the thin filament. In the model simulations, the time to 50% relaxation (t(R50)) increased over the range of sarcomere lengths from 1.9 μm to 2.2 μm by 0.11s, comparable to the increased duration of 0.12s shown in experiments. Model simulated t(R50) increased by 0.12s over the range of peak intracellular calcium concentrations from 0.87 μM to 1.45 μM. Our simulation results suggest that the prolongation of contraction at higher tension is a result of the tighter binding of Ca(2+) to troponin in areas under higher tension, thus delaying the deactivation of the troponin. Public Library of Science 2018-10-04 /pmc/articles/PMC6171862/ /pubmed/30286135 http://dx.doi.org/10.1371/journal.pone.0204642 Text en © 2018 Dupuis et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Dupuis, Lauren J. Lumens, Joost Arts, Theo Delhaas, Tammo High tension in sarcomeres hinders myocardial relaxation: A computational study |
title | High tension in sarcomeres hinders myocardial relaxation: A computational study |
title_full | High tension in sarcomeres hinders myocardial relaxation: A computational study |
title_fullStr | High tension in sarcomeres hinders myocardial relaxation: A computational study |
title_full_unstemmed | High tension in sarcomeres hinders myocardial relaxation: A computational study |
title_short | High tension in sarcomeres hinders myocardial relaxation: A computational study |
title_sort | high tension in sarcomeres hinders myocardial relaxation: a computational study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171862/ https://www.ncbi.nlm.nih.gov/pubmed/30286135 http://dx.doi.org/10.1371/journal.pone.0204642 |
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