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Effects of Chronic Administration of Clenbuterol on Contractile Properties and Calcium Homeostasis in Rat Extensor Digitorum Longus Muscle
Clenbuterol, a β(2)-agonist, induces skeletal muscle hypertrophy and a shift from slow-oxidative to fast-glycolytic muscle fiber type profile. However, the cellular mechanisms of the effects of chronic clenbuterol administration on skeletal muscle are not completely understood. As the intracellular...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074032/ https://www.ncbi.nlm.nih.gov/pubmed/24971566 http://dx.doi.org/10.1371/journal.pone.0100281 |
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author | Sirvent, Pascal Douillard, Aymerick Galbes, Olivier Ramonatxo, Christelle Py, Guillaume Candau, Robin Lacampagne, Alain |
author_facet | Sirvent, Pascal Douillard, Aymerick Galbes, Olivier Ramonatxo, Christelle Py, Guillaume Candau, Robin Lacampagne, Alain |
author_sort | Sirvent, Pascal |
collection | PubMed |
description | Clenbuterol, a β(2)-agonist, induces skeletal muscle hypertrophy and a shift from slow-oxidative to fast-glycolytic muscle fiber type profile. However, the cellular mechanisms of the effects of chronic clenbuterol administration on skeletal muscle are not completely understood. As the intracellular Ca(2+) concentration must be finely regulated in many cellular processes, the aim of this study was to investigate the effects of chronic clenbuterol treatment on force, fatigue, intracellular calcium (Ca(2+)) homeostasis and Ca(2+)-dependent proteolysis in fast-twitch skeletal muscles (the extensor digitorum longus, EDL, muscle), as they are more sensitive to clenbuterol-induced hypertrophy. Male Wistar rats were chronically treated with 4 mg.kg(−1) clenbuterol or saline vehicle (controls) for 21 days. Confocal microscopy was used to evaluate sarcoplasmic reticulum Ca(2+) load, Ca(2+) -transient amplitude and Ca(2+) spark properties. EDL muscles from clenbuterol-treated animals displayed hypertrophy, a shift from slow to fast fiber type profile and increased absolute force, while the relative force remained unchanged and resistance to fatigue decreased compared to control muscles from rats treated with saline vehicle. Compared to control animals, clenbuterol treatment decreased Ca(2+)-transient amplitude, Ca(2+) spark amplitude and frequency and the sarcoplasmic reticulum Ca(2+) load was markedly reduced. Conversely, calpain activity was increased by clenbuterol chronic treatment. These results indicate that chronic treatment with clenbuterol impairs Ca(2+) homeostasis and this could contribute to the remodeling and functional impairment of fast-twitch skeletal muscle. |
format | Online Article Text |
id | pubmed-4074032 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40740322014-07-02 Effects of Chronic Administration of Clenbuterol on Contractile Properties and Calcium Homeostasis in Rat Extensor Digitorum Longus Muscle Sirvent, Pascal Douillard, Aymerick Galbes, Olivier Ramonatxo, Christelle Py, Guillaume Candau, Robin Lacampagne, Alain PLoS One Research Article Clenbuterol, a β(2)-agonist, induces skeletal muscle hypertrophy and a shift from slow-oxidative to fast-glycolytic muscle fiber type profile. However, the cellular mechanisms of the effects of chronic clenbuterol administration on skeletal muscle are not completely understood. As the intracellular Ca(2+) concentration must be finely regulated in many cellular processes, the aim of this study was to investigate the effects of chronic clenbuterol treatment on force, fatigue, intracellular calcium (Ca(2+)) homeostasis and Ca(2+)-dependent proteolysis in fast-twitch skeletal muscles (the extensor digitorum longus, EDL, muscle), as they are more sensitive to clenbuterol-induced hypertrophy. Male Wistar rats were chronically treated with 4 mg.kg(−1) clenbuterol or saline vehicle (controls) for 21 days. Confocal microscopy was used to evaluate sarcoplasmic reticulum Ca(2+) load, Ca(2+) -transient amplitude and Ca(2+) spark properties. EDL muscles from clenbuterol-treated animals displayed hypertrophy, a shift from slow to fast fiber type profile and increased absolute force, while the relative force remained unchanged and resistance to fatigue decreased compared to control muscles from rats treated with saline vehicle. Compared to control animals, clenbuterol treatment decreased Ca(2+)-transient amplitude, Ca(2+) spark amplitude and frequency and the sarcoplasmic reticulum Ca(2+) load was markedly reduced. Conversely, calpain activity was increased by clenbuterol chronic treatment. These results indicate that chronic treatment with clenbuterol impairs Ca(2+) homeostasis and this could contribute to the remodeling and functional impairment of fast-twitch skeletal muscle. Public Library of Science 2014-06-27 /pmc/articles/PMC4074032/ /pubmed/24971566 http://dx.doi.org/10.1371/journal.pone.0100281 Text en © 2014 Sirvent 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Sirvent, Pascal Douillard, Aymerick Galbes, Olivier Ramonatxo, Christelle Py, Guillaume Candau, Robin Lacampagne, Alain Effects of Chronic Administration of Clenbuterol on Contractile Properties and Calcium Homeostasis in Rat Extensor Digitorum Longus Muscle |
title | Effects of Chronic Administration of Clenbuterol on Contractile Properties and Calcium Homeostasis in Rat Extensor Digitorum Longus Muscle |
title_full | Effects of Chronic Administration of Clenbuterol on Contractile Properties and Calcium Homeostasis in Rat Extensor Digitorum Longus Muscle |
title_fullStr | Effects of Chronic Administration of Clenbuterol on Contractile Properties and Calcium Homeostasis in Rat Extensor Digitorum Longus Muscle |
title_full_unstemmed | Effects of Chronic Administration of Clenbuterol on Contractile Properties and Calcium Homeostasis in Rat Extensor Digitorum Longus Muscle |
title_short | Effects of Chronic Administration of Clenbuterol on Contractile Properties and Calcium Homeostasis in Rat Extensor Digitorum Longus Muscle |
title_sort | effects of chronic administration of clenbuterol on contractile properties and calcium homeostasis in rat extensor digitorum longus muscle |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074032/ https://www.ncbi.nlm.nih.gov/pubmed/24971566 http://dx.doi.org/10.1371/journal.pone.0100281 |
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