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Distinct contributions of the thin and thick filaments to length-dependent activation in heart muscle

The Frank-Starling relation is a fundamental auto-regulatory property of the heart that ensures the volume of blood ejected in each heartbeat is matched to the extent of venous filling. At the cellular level, heart muscle cells generate higher force when stretched, but despite intense efforts the un...

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Autores principales: Zhang, Xuemeng, Kampourakis, Thomas, Yan, Ziqian, Sevrieva, Ivanka, Irving, Malcolm, Sun, Yin-Biao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5365314/
https://www.ncbi.nlm.nih.gov/pubmed/28229860
http://dx.doi.org/10.7554/eLife.24081
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author Zhang, Xuemeng
Kampourakis, Thomas
Yan, Ziqian
Sevrieva, Ivanka
Irving, Malcolm
Sun, Yin-Biao
author_facet Zhang, Xuemeng
Kampourakis, Thomas
Yan, Ziqian
Sevrieva, Ivanka
Irving, Malcolm
Sun, Yin-Biao
author_sort Zhang, Xuemeng
collection PubMed
description The Frank-Starling relation is a fundamental auto-regulatory property of the heart that ensures the volume of blood ejected in each heartbeat is matched to the extent of venous filling. At the cellular level, heart muscle cells generate higher force when stretched, but despite intense efforts the underlying molecular mechanism remains unknown. We applied a fluorescence-based method, which reports structural changes separately in the thick and thin filaments of rat cardiac muscle, to elucidate that mechanism. The distinct structural changes of troponin C in the thin filaments and myosin regulatory light chain in the thick filaments allowed us to identify two aspects of the Frank-Starling relation. Our results show that the enhanced force observed when heart muscle cells are maximally activated by calcium is due to a change in thick filament structure, but the increase in calcium sensitivity at lower calcium levels is due to a change in thin filament structure. DOI: http://dx.doi.org/10.7554/eLife.24081.001
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spelling pubmed-53653142017-03-27 Distinct contributions of the thin and thick filaments to length-dependent activation in heart muscle Zhang, Xuemeng Kampourakis, Thomas Yan, Ziqian Sevrieva, Ivanka Irving, Malcolm Sun, Yin-Biao eLife Biophysics and Structural Biology The Frank-Starling relation is a fundamental auto-regulatory property of the heart that ensures the volume of blood ejected in each heartbeat is matched to the extent of venous filling. At the cellular level, heart muscle cells generate higher force when stretched, but despite intense efforts the underlying molecular mechanism remains unknown. We applied a fluorescence-based method, which reports structural changes separately in the thick and thin filaments of rat cardiac muscle, to elucidate that mechanism. The distinct structural changes of troponin C in the thin filaments and myosin regulatory light chain in the thick filaments allowed us to identify two aspects of the Frank-Starling relation. Our results show that the enhanced force observed when heart muscle cells are maximally activated by calcium is due to a change in thick filament structure, but the increase in calcium sensitivity at lower calcium levels is due to a change in thin filament structure. DOI: http://dx.doi.org/10.7554/eLife.24081.001 eLife Sciences Publications, Ltd 2017-02-23 /pmc/articles/PMC5365314/ /pubmed/28229860 http://dx.doi.org/10.7554/eLife.24081 Text en © 2017, Zhang et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biophysics and Structural Biology
Zhang, Xuemeng
Kampourakis, Thomas
Yan, Ziqian
Sevrieva, Ivanka
Irving, Malcolm
Sun, Yin-Biao
Distinct contributions of the thin and thick filaments to length-dependent activation in heart muscle
title Distinct contributions of the thin and thick filaments to length-dependent activation in heart muscle
title_full Distinct contributions of the thin and thick filaments to length-dependent activation in heart muscle
title_fullStr Distinct contributions of the thin and thick filaments to length-dependent activation in heart muscle
title_full_unstemmed Distinct contributions of the thin and thick filaments to length-dependent activation in heart muscle
title_short Distinct contributions of the thin and thick filaments to length-dependent activation in heart muscle
title_sort distinct contributions of the thin and thick filaments to length-dependent activation in heart muscle
topic Biophysics and Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5365314/
https://www.ncbi.nlm.nih.gov/pubmed/28229860
http://dx.doi.org/10.7554/eLife.24081
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