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X-ROS Signaling Depends on Length-Dependent Calcium Buffering by Troponin

The stretching of a cardiomyocyte leads to the increased production of reactive oxygen species that increases ryanodine receptor open probability through a process termed X-ROS signaling. The stretching of the myocyte also increases the calcium affinity of myofilament Troponin C, which increases its...

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Autores principales: Limbu, Sarita, Prosser, Benjamin L., Lederer, William J., Ward, Christopher W., Jafri, Mohsin S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152234/
https://www.ncbi.nlm.nih.gov/pubmed/34068012
http://dx.doi.org/10.3390/cells10051189
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author Limbu, Sarita
Prosser, Benjamin L.
Lederer, William J.
Ward, Christopher W.
Jafri, Mohsin S.
author_facet Limbu, Sarita
Prosser, Benjamin L.
Lederer, William J.
Ward, Christopher W.
Jafri, Mohsin S.
author_sort Limbu, Sarita
collection PubMed
description The stretching of a cardiomyocyte leads to the increased production of reactive oxygen species that increases ryanodine receptor open probability through a process termed X-ROS signaling. The stretching of the myocyte also increases the calcium affinity of myofilament Troponin C, which increases its calcium buffering capacity. Here, an integrative experimental and modeling study is pursued to explain the interplay of length-dependent changes in calcium buffering by troponin and stretch-activated X-ROS calcium signaling. Using this combination, we show that the troponin C-dependent increase in myoplasmic calcium buffering during myocyte stretching largely offsets the X-ROS-dependent increase in calcium release from the sarcoplasmic reticulum. The combination of modeling and experiment are further informed by the elimination of length-dependent changes to troponin C calcium binding in the presence of blebbistatin. Here, the model suggests that it is the X-ROS signaling-dependent Ca(2+) release increase that serves to maintain free myoplasmic calcium concentrations during a change in myocyte length. Together, our experimental and modeling approaches have further defined the relative contributions of X-ROS signaling and the length-dependent calcium buffering by troponin in shaping the myoplasmic calcium transient.
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spelling pubmed-81522342021-05-27 X-ROS Signaling Depends on Length-Dependent Calcium Buffering by Troponin Limbu, Sarita Prosser, Benjamin L. Lederer, William J. Ward, Christopher W. Jafri, Mohsin S. Cells Article The stretching of a cardiomyocyte leads to the increased production of reactive oxygen species that increases ryanodine receptor open probability through a process termed X-ROS signaling. The stretching of the myocyte also increases the calcium affinity of myofilament Troponin C, which increases its calcium buffering capacity. Here, an integrative experimental and modeling study is pursued to explain the interplay of length-dependent changes in calcium buffering by troponin and stretch-activated X-ROS calcium signaling. Using this combination, we show that the troponin C-dependent increase in myoplasmic calcium buffering during myocyte stretching largely offsets the X-ROS-dependent increase in calcium release from the sarcoplasmic reticulum. The combination of modeling and experiment are further informed by the elimination of length-dependent changes to troponin C calcium binding in the presence of blebbistatin. Here, the model suggests that it is the X-ROS signaling-dependent Ca(2+) release increase that serves to maintain free myoplasmic calcium concentrations during a change in myocyte length. Together, our experimental and modeling approaches have further defined the relative contributions of X-ROS signaling and the length-dependent calcium buffering by troponin in shaping the myoplasmic calcium transient. MDPI 2021-05-13 /pmc/articles/PMC8152234/ /pubmed/34068012 http://dx.doi.org/10.3390/cells10051189 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Limbu, Sarita
Prosser, Benjamin L.
Lederer, William J.
Ward, Christopher W.
Jafri, Mohsin S.
X-ROS Signaling Depends on Length-Dependent Calcium Buffering by Troponin
title X-ROS Signaling Depends on Length-Dependent Calcium Buffering by Troponin
title_full X-ROS Signaling Depends on Length-Dependent Calcium Buffering by Troponin
title_fullStr X-ROS Signaling Depends on Length-Dependent Calcium Buffering by Troponin
title_full_unstemmed X-ROS Signaling Depends on Length-Dependent Calcium Buffering by Troponin
title_short X-ROS Signaling Depends on Length-Dependent Calcium Buffering by Troponin
title_sort x-ros signaling depends on length-dependent calcium buffering by troponin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152234/
https://www.ncbi.nlm.nih.gov/pubmed/34068012
http://dx.doi.org/10.3390/cells10051189
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AT wardchristopherw xrossignalingdependsonlengthdependentcalciumbufferingbytroponin
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