Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Sirvent, Pascal, Douillard, Aymerick, Galbes, Olivier, Ramonatxo, Christelle, Py, Guillaume, Candau, Robin, Lacampagne, Alain
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
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
_version_ 1782323164867461120
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
work_keys_str_mv AT sirventpascal effectsofchronicadministrationofclenbuteroloncontractilepropertiesandcalciumhomeostasisinratextensordigitorumlongusmuscle
AT douillardaymerick effectsofchronicadministrationofclenbuteroloncontractilepropertiesandcalciumhomeostasisinratextensordigitorumlongusmuscle
AT galbesolivier effectsofchronicadministrationofclenbuteroloncontractilepropertiesandcalciumhomeostasisinratextensordigitorumlongusmuscle
AT ramonatxochristelle effectsofchronicadministrationofclenbuteroloncontractilepropertiesandcalciumhomeostasisinratextensordigitorumlongusmuscle
AT pyguillaume effectsofchronicadministrationofclenbuteroloncontractilepropertiesandcalciumhomeostasisinratextensordigitorumlongusmuscle
AT candaurobin effectsofchronicadministrationofclenbuteroloncontractilepropertiesandcalciumhomeostasisinratextensordigitorumlongusmuscle
AT lacampagnealain effectsofchronicadministrationofclenbuteroloncontractilepropertiesandcalciumhomeostasisinratextensordigitorumlongusmuscle