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Myosin-binding protein C corrects an intrinsic inhomogeneity in cardiac excitation-contraction coupling

The beating heart exhibits remarkable contractile fidelity over a lifetime, which reflects the tight coupling of electrical, chemical, and mechanical elements within the sarcomere, the elementary contractile unit. On a beat-to-beat basis, calcium is released from the ends of the sarcomere and must d...

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Autores principales: Previs, Michael J., Prosser, Benjamin L., Mun, Ji Young, Previs, Samantha Beck, Gulick, James, Lee, Kyounghwan, Robbins, Jeffrey, Craig, Roger, Lederer, W. J., Warshaw, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380226/
https://www.ncbi.nlm.nih.gov/pubmed/25839057
http://dx.doi.org/10.1126/sciadv.1400205
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author Previs, Michael J.
Prosser, Benjamin L.
Mun, Ji Young
Previs, Samantha Beck
Gulick, James
Lee, Kyounghwan
Robbins, Jeffrey
Craig, Roger
Lederer, W. J.
Warshaw, David M.
author_facet Previs, Michael J.
Prosser, Benjamin L.
Mun, Ji Young
Previs, Samantha Beck
Gulick, James
Lee, Kyounghwan
Robbins, Jeffrey
Craig, Roger
Lederer, W. J.
Warshaw, David M.
author_sort Previs, Michael J.
collection PubMed
description The beating heart exhibits remarkable contractile fidelity over a lifetime, which reflects the tight coupling of electrical, chemical, and mechanical elements within the sarcomere, the elementary contractile unit. On a beat-to-beat basis, calcium is released from the ends of the sarcomere and must diffuse toward the sarcomere center to fully activate the myosin- and actin-based contractile proteins. The resultant spatial and temporal gradient in free calcium across the sarcomere should lead to nonuniform and inefficient activation of contraction. We show that myosin-binding protein C (MyBP-C), through its positioning on the myosin thick filaments, corrects this nonuniformity in calcium activation by exquisitely sensitizing the contractile apparatus to calcium in a manner that precisely counterbalances the calcium gradient. Thus, the presence and correct localization of MyBP-C within the sarcomere is critically important for normal cardiac function, and any disturbance of MyBP-C localization or function will contribute to the consequent cardiac pathologies.
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spelling pubmed-43802262015-03-31 Myosin-binding protein C corrects an intrinsic inhomogeneity in cardiac excitation-contraction coupling Previs, Michael J. Prosser, Benjamin L. Mun, Ji Young Previs, Samantha Beck Gulick, James Lee, Kyounghwan Robbins, Jeffrey Craig, Roger Lederer, W. J. Warshaw, David M. Sci Adv Research Articles The beating heart exhibits remarkable contractile fidelity over a lifetime, which reflects the tight coupling of electrical, chemical, and mechanical elements within the sarcomere, the elementary contractile unit. On a beat-to-beat basis, calcium is released from the ends of the sarcomere and must diffuse toward the sarcomere center to fully activate the myosin- and actin-based contractile proteins. The resultant spatial and temporal gradient in free calcium across the sarcomere should lead to nonuniform and inefficient activation of contraction. We show that myosin-binding protein C (MyBP-C), through its positioning on the myosin thick filaments, corrects this nonuniformity in calcium activation by exquisitely sensitizing the contractile apparatus to calcium in a manner that precisely counterbalances the calcium gradient. Thus, the presence and correct localization of MyBP-C within the sarcomere is critically important for normal cardiac function, and any disturbance of MyBP-C localization or function will contribute to the consequent cardiac pathologies. American Association for the Advancement of Science 2015-02-20 /pmc/articles/PMC4380226/ /pubmed/25839057 http://dx.doi.org/10.1126/sciadv.1400205 Text en Copyright © 2015, The Authors http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Previs, Michael J.
Prosser, Benjamin L.
Mun, Ji Young
Previs, Samantha Beck
Gulick, James
Lee, Kyounghwan
Robbins, Jeffrey
Craig, Roger
Lederer, W. J.
Warshaw, David M.
Myosin-binding protein C corrects an intrinsic inhomogeneity in cardiac excitation-contraction coupling
title Myosin-binding protein C corrects an intrinsic inhomogeneity in cardiac excitation-contraction coupling
title_full Myosin-binding protein C corrects an intrinsic inhomogeneity in cardiac excitation-contraction coupling
title_fullStr Myosin-binding protein C corrects an intrinsic inhomogeneity in cardiac excitation-contraction coupling
title_full_unstemmed Myosin-binding protein C corrects an intrinsic inhomogeneity in cardiac excitation-contraction coupling
title_short Myosin-binding protein C corrects an intrinsic inhomogeneity in cardiac excitation-contraction coupling
title_sort myosin-binding protein c corrects an intrinsic inhomogeneity in cardiac excitation-contraction coupling
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380226/
https://www.ncbi.nlm.nih.gov/pubmed/25839057
http://dx.doi.org/10.1126/sciadv.1400205
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