Modeling autoregulation of cardiac excitation-Ca-contraction and arrhythmogenic activities in response to mechanical load changes
Summary: The heart has intrinsic abilities to autoregulate contractile force in response to mechanical load. Recent experimental studies show that cardiomyocytes have mechano-chemo-transduction (MCT) mechanisms that form a closed feedback loop in the excitation-Ca2+ signaling-contraction (E-C) coupl...
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| Language: | English |
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Elsevier
2025-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225000471 |
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| author | Asuka Hatano Leighton T. Izu Ye Chen-Izu Daisuke Sato |
| author_facet | Asuka Hatano Leighton T. Izu Ye Chen-Izu Daisuke Sato |
| author_sort | Asuka Hatano |
| collection | DOAJ |
| description | Summary: The heart has intrinsic abilities to autoregulate contractile force in response to mechanical load. Recent experimental studies show that cardiomyocytes have mechano-chemo-transduction (MCT) mechanisms that form a closed feedback loop in the excitation-Ca2+ signaling-contraction (E-C) coupling. This closed feedback loop enables autoregulation of contraction in response to mechanical load changes. Here, we develop the first autoregulatory E-C coupling model that couples electrophysiology, Ca2+ signaling, force development and contraction, and MCT feedback. The model recapitulates the experimental data showing that the mechanical load on cardiomyocytes during contraction increases the L-type Ca2+ current, action potential duration, sarcoplasmic reticulum (SR) Ca2+ content, and SR Ca2+ release, giving rise to increased cytosolic Ca2+ transient (MCT-Ca2+ gain) and enhanced contraction. The model also makes non-trivial predictions on the autoregulation of contraction with moderate MCT-Ca2+ gain under a range of physiological load changes, but arrhythmogenic discordant alternans with excessive MCT-Ca2+ gain under pathological overload. |
| format | Article |
| id | doaj-art-420a43d9372145d18f2da3626dfacfd5 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-420a43d9372145d18f2da3626dfacfd52025-01-29T05:01:37ZengElsevieriScience2589-00422025-02-01282111788Modeling autoregulation of cardiac excitation-Ca-contraction and arrhythmogenic activities in response to mechanical load changesAsuka Hatano0Leighton T. Izu1Ye Chen-Izu2Daisuke Sato3Department of Pharmacology, University of California – Davis, Davis, CA 94040, USA; Department of Mechanical Engineering, University of Tokyo, Tokyo 113-8656, Japan; Corresponding authorDepartment of Pharmacology, University of California – Davis, Davis, CA 94040, USA; Corresponding authorDepartment of Pharmacology, University of California – Davis, Davis, CA 94040, USA; Department of Biomedical Engineering, University of California – Davis, Davis, CA 94040, USA; Department of Internal Medicine/Cardiology, University of California – Davis, Davis, CA 94040, USADepartment of Pharmacology, University of California – Davis, Davis, CA 94040, USASummary: The heart has intrinsic abilities to autoregulate contractile force in response to mechanical load. Recent experimental studies show that cardiomyocytes have mechano-chemo-transduction (MCT) mechanisms that form a closed feedback loop in the excitation-Ca2+ signaling-contraction (E-C) coupling. This closed feedback loop enables autoregulation of contraction in response to mechanical load changes. Here, we develop the first autoregulatory E-C coupling model that couples electrophysiology, Ca2+ signaling, force development and contraction, and MCT feedback. The model recapitulates the experimental data showing that the mechanical load on cardiomyocytes during contraction increases the L-type Ca2+ current, action potential duration, sarcoplasmic reticulum (SR) Ca2+ content, and SR Ca2+ release, giving rise to increased cytosolic Ca2+ transient (MCT-Ca2+ gain) and enhanced contraction. The model also makes non-trivial predictions on the autoregulation of contraction with moderate MCT-Ca2+ gain under a range of physiological load changes, but arrhythmogenic discordant alternans with excessive MCT-Ca2+ gain under pathological overload.http://www.sciencedirect.com/science/article/pii/S2589004225000471cardiovascular medicinecell biologybioinformatics |
| spellingShingle | Asuka Hatano Leighton T. Izu Ye Chen-Izu Daisuke Sato Modeling autoregulation of cardiac excitation-Ca-contraction and arrhythmogenic activities in response to mechanical load changes iScience cardiovascular medicine cell biology bioinformatics |
| title | Modeling autoregulation of cardiac excitation-Ca-contraction and arrhythmogenic activities in response to mechanical load changes |
| title_full | Modeling autoregulation of cardiac excitation-Ca-contraction and arrhythmogenic activities in response to mechanical load changes |
| title_fullStr | Modeling autoregulation of cardiac excitation-Ca-contraction and arrhythmogenic activities in response to mechanical load changes |
| title_full_unstemmed | Modeling autoregulation of cardiac excitation-Ca-contraction and arrhythmogenic activities in response to mechanical load changes |
| title_short | Modeling autoregulation of cardiac excitation-Ca-contraction and arrhythmogenic activities in response to mechanical load changes |
| title_sort | modeling autoregulation of cardiac excitation ca contraction and arrhythmogenic activities in response to mechanical load changes |
| topic | cardiovascular medicine cell biology bioinformatics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225000471 |
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