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Effects of chronic administration of clenbuterol on contractile properties and calcium homeostasis in rat extensor digitorum longus muscle

PloS one, 2014-06, Vol.9 (6), p.e100281-e100281 [Peer Reviewed Journal]

2014 Sirvent et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;Distributed under a Creative Commons Attribution 4.0 International License ;2014 Sirvent et al 2014 Sirvent et al ;ISSN: 1932-6203 ;EISSN: 1932-6203 ;DOI: 10.1371/journal.pone.0100281 ;PMID: 24971566

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Title:
Effects of chronic administration of clenbuterol on contractile properties and calcium homeostasis in rat extensor digitorum longus muscle
Author: Sirvent, Pascal ; Douillard, Aymerick ; Galbes, Olivier ; Ramonatxo, Christelle ; Py, Guillaume ; Candau, Robin ; Lacampagne, Alain
Csernoch, Laszlo
Subjects: Adrenergic beta-Agonists - administration & dosage ; Animals ; Biology and Life Sciences ; Calcium ; Calcium (intracellular) ; Calcium (reticular) ; Calcium - metabolism ; Calcium homeostasis ; Calcium Signaling ; Calcium signalling ; Calpain ; Calpain - metabolism ; Clenbuterol ; Clenbuterol - administration & dosage ; Confocal ; Confocal microscopy ; Fatigue ; Genotype & phenotype ; Glycolysis ; Homeostasis ; Homeostasis - drug effects ; Hypertrophy ; Intracellular ; Laboratory animals ; Life Sciences ; Male ; Medicine and Health Sciences ; Metabolism ; Microscopy ; Muscle contraction ; Muscle Contraction - drug effects ; Muscle Fibers, Fast-Twitch - drug effects ; Muscle Fibers, Fast-Twitch - physiology ; Muscle, Skeletal - cytology ; Muscle, Skeletal - drug effects ; Muscle, Skeletal - physiology ; Muscles ; Muscular fatigue ; Musculoskeletal system ; Pharmacology ; Phenotype ; Physiology ; Proteins ; Proteolysis ; Rats ; Research and Analysis Methods ; Rodents ; Sarcoplasmic reticulum ; Sarcoplasmic Reticulum - drug effects ; Sarcoplasmic Reticulum - metabolism ; Skeletal muscle ; Studies
Is Part Of: PloS one, 2014-06, Vol.9 (6), p.e100281-e100281
Description: Clenbuterol, a β2-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 Ca2+ 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 (Ca2+) homeostasis and Ca2+-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 Ca2+ load, Ca2+-transient amplitude and Ca2+ 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 Ca2+-transient amplitude, Ca2+ spark amplitude and frequency and the sarcoplasmic reticulum Ca2+ load was markedly reduced. Conversely, calpain activity was increased by clenbuterol chronic treatment. These results indicate that chronic treatment with clenbuterol impairs Ca2+ homeostasis and this could contribute to the remodeling and functional impairment of fast-twitch skeletal muscle.
Publisher: United States: Public Library of Science
Language: English
Identifier: ISSN: 1932-6203
EISSN: 1932-6203
DOI: 10.1371/journal.pone.0100281
PMID: 24971566
Source: Geneva Foundation Free Medical Journals at publisher websites
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Effects of chronic administration of clenbuterol on contractile properties and calcium homeostasis in rat extensor digitorum longus muscle

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