Effects of Chronic Administration of Clenbuterol on Contractile Properties and Calcium Homeostasis in Rat Extensor Digitorum Longus Muscle
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{"title"=>"Effects of chronic administration of clenbuterol on contractile properties and calcium homeostasis in rat extensor digitorum longus muscle", "type"=>"journal", "authors"=>[{"first_name"=>"Pascal", "last_name"=>"Sirvent", "scopus_author_id"=>"9242425900"}, {"first_name"=>"Aymerick", "last_name"=>"Douillard", "scopus_author_id"=>"56855933500"}, {"first_name"=>"Olivier", "last_name"=>"Galbes", "scopus_author_id"=>"24175574400"}, {"first_name"=>"Christelle", "last_name"=>"Ramonatxo", "scopus_author_id"=>"26639787300"}, {"first_name"=>"Guillaume", "last_name"=>"Py", "scopus_author_id"=>"6602358260"}, {"first_name"=>"Robin", "last_name"=>"Candau", "scopus_author_id"=>"8604260400"}, {"first_name"=>"Alain", "last_name"=>"Lacampagne", "scopus_author_id"=>"6603756919"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"373428602", "sgr"=>"84903641293", "issn"=>"19326203", "pmid"=>"24971566", "scopus"=>"2-s2.0-84903641293", "doi"=>"10.1371/journal.pone.0100281"}, "id"=>"a831dcc1-4131-3cf2-a10c-134e9bf1c4da", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/effects-chronic-administration-clenbuterol-contractile-properties-calcium-homeostasis-rat-extensor-d", "reader_count"=>13, "reader_count_by_academic_status"=>{"Researcher"=>3, "Student > Ph. D. Student"=>4, "Student > Master"=>2, "Other"=>2, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Researcher"=>3, "Student > Ph. D. Student"=>4, "Student > Master"=>2, "Other"=>2, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>2, "Agricultural and Biological Sciences"=>4, "Sports and Recreations"=>5}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Sports and Recreations"=>{"Sports and Recreations"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "reader_count_by_country"=>{"Italy"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1570125"], "description"=>"<p><b>A,</b> Representative line-scan Δ<i>F</i>/<i>F</i> images of permeabilized skeletal muscle fibers from control (top) and clenbuterol-treated rats (bottom). <b>B,</b> Comparison of Ca<sup>2+</sup>-spark amplitude in control (white bar graph) and clenbuterol-treated (black bar graph) animals. * p<0.05 compared to controls. <b>C,</b> Comparison of Ca<sup>2+</sup>-spark frequency in control (white bar graph) and clenbuterol-treated (black bar graph) animals. Values are expressed as the mean ± SEM of 10 animals/group. * p<0.05 compared to controls.</p>", "links"=>[], "tags"=>["anatomy", "Musculoskeletal system", "muscles", "cell biology", "Signal transduction", "cell signaling", "Signaling cascades", "Calcium signaling cascade", "Calcium signaling", "Calcium-mediated signal transduction", "Molecular cell biology", "organisms", "animals", "vertebrates", "mammals", "rodents", "rats", "physiology", "Muscle physiology", "Muscle biochemistry", "Muscle functions", "systems biology", "Integrative physiology", "health care", "physiotherapy", "Sports and exercise medicine", "Model organisms", "Animal models", "clenbuterol", "amplitude"], "article_id"=>1086976, "categories"=>["Biological Sciences"], "users"=>["Pascal Sirvent", "Aymerick Douillard", "Olivier Galbes", "Christelle Ramonatxo", "Guillaume Py", "Robin Candau", "Alain Lacampagne"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100281.g003", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_chronic_clenbuterol_treatment_on_Ca_2_spark_amplitude_and_frequency_/1086976", "title"=>"Effects of chronic clenbuterol treatment on Ca<sup>2+</sup> spark amplitude and frequency.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-27 02:47:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/1570122"], "description"=>"<p><b>A,</b> Histochemical staining for Myosin ATPase in 6 µm EDL cryosections from control (CTR; untreated group) and clenbuterol-treated (CLB) animals. The images correspond to staining for ATPase activity. The dark stain highlights fibers that mainly express Myosin Heavy Chain-I (MyHC-I); the light stain indicates fibers that mainly express MyHC-IIa; and the intermediate color corresponds to fibers that mainly express MyHC-IIx-IIb. <b>B,</b> Quantification of Myosin ATPase staining revealed an increased cross-sectional area for all fiber types following clenbuterol treatment (In µm<sup>2</sup>, type I from 689.52±29.56 to 828.53±35.96, type IIa from 860.84±40.37 to 1009.43±54.18, type IIx-b from 1968.74±111.39 to 3390.55±173.64). * p<0.05 compared to CTR. <b>C,</b> Treatment with clenbuterol induced a phenotypic shift from slow-oxidative to fast-glycolytic profile (type I from xxx ± xx to xxx ± xx, type IIa from xxx ± xx to xxx ± xx, type IIx-b from xx ± xx to xxx ± xx). Values are expressed as the mean ± SEM (7 animals in each group). * p<0.05 compared to CTR.</p>", "links"=>[], "tags"=>["anatomy", "Musculoskeletal system", "muscles", "cell biology", "Signal transduction", "cell signaling", "Signaling cascades", "Calcium signaling cascade", "Calcium signaling", "Calcium-mediated signal transduction", "Molecular cell biology", "organisms", "animals", "vertebrates", "mammals", "rodents", "rats", "physiology", "Muscle physiology", "Muscle biochemistry", "Muscle functions", "systems biology", "Integrative physiology", "health care", "physiotherapy", "Sports and exercise medicine", "Model organisms", "Animal models", "clenbuterol", "edl", "fiber-type", "muscle-fiber", "cross-sectional"], "article_id"=>1086973, "categories"=>["Biological Sciences"], "users"=>["Pascal Sirvent", "Aymerick Douillard", "Olivier Galbes", "Christelle Ramonatxo", "Guillaume Py", "Robin Candau", "Alain Lacampagne"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100281.g001", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_chronic_clenbuterol_treatment_on_EDL_fiber_type_profile_and_muscle_fiber_cross_sectional_area_/1086973", "title"=>"Effects of chronic clenbuterol treatment on EDL fiber-type profile and muscle-fiber cross-sectional area.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-27 02:47:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/1570126"], "description"=>"<p><b>A,</b> Typical representation of calcium release elicited with 50 µM 4-chloro-<i>m</i>-cresol in control (CTR) and clenbuterol-treated (CLB) animals. Ca<sup>2+</sup>-transient was imaged using fast time series of x–y confocal images. The amplitude (peak) of the signal was used as indicator of SR Ca<sup>2+</sup> load. <b>B,</b> Typical representation of Ca<sup>2+</sup>-transient triggered by field stimulation with a single 2 ms pulse in intact EDL muscles loaded with 50 µM Rhod-2 AM from control (CTR) and clenbuterol-treated (CLB) animals. <b>C,</b> Comparison of SR Ca<sup>2+</sup>-load in control (CTR) and clenbuterol-treated (CLB) a nimals. Ca<sup>2+</sup> release was elicited with 50 µM 4-chloro-m-cresol as shown in panel A. Values are expressed as the mean ± SEM of 10 animals in each group. * p<0.05 compared to controls. <b>D,</b> Quantification of Ca<sup>2+</sup>-transient amplitude in control (CTR) and clenbuterol-treated (CLB) animals. Ca<sup>2+</sup>-transients were triggered by field stimulation with a single 2 ms pulse as shown in panel B. Values are expressed as the mean ± SEM of 8 animals in each group. * p<0.05 compared to controls.</p>", "links"=>[], "tags"=>["anatomy", "Musculoskeletal system", "muscles", "cell biology", "Signal transduction", "cell signaling", "Signaling cascades", "Calcium signaling cascade", "Calcium signaling", "Calcium-mediated signal transduction", "Molecular cell biology", "organisms", "animals", "vertebrates", "mammals", "rodents", "rats", "physiology", "Muscle physiology", "Muscle biochemistry", "Muscle functions", "systems biology", "Integrative physiology", "health care", "physiotherapy", "Sports and exercise medicine", "Model organisms", "Animal models", "clenbuterol", "sr"], "article_id"=>1086977, "categories"=>["Biological Sciences"], "users"=>["Pascal Sirvent", "Aymerick Douillard", "Olivier Galbes", "Christelle Ramonatxo", "Guillaume Py", "Robin Candau", "Alain Lacampagne"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100281.g004", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_chronic_clenbuterol_treatment_on_SR_Ca_2_load_and_Ca_2_transient_amplitude_/1086977", "title"=>"Effects of chronic clenbuterol treatment on SR Ca<sup>2+</sup> load and Ca<sup>2+</sup>-transient amplitude.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-27 02:47:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/1570127"], "description"=>"<p><b>A,</b> Calpain activity was determined in whole EDL muscle homogenates using a calpain-specific fluorogenic substrate in control (CTR) and clenbuterol-treated (CLB) animals. * p<0.05 compared to controls. <b>B,</b> Western blot analysis with polyclonal anti-calpain 1 and polyclonal anti-calpain 2 antibodies of EDL muscle homogenates from control (CTR) and clenbuterol-treated (CLB) animals. <b>C,</b> Calculation of the calpain fractional activation index (i.e., percentage of autolysed calpains) in EDL muscle homogenates from control (CTR) and clenbuterol treated (CLB) animals. Values are the mean ± SEM of 8 animals in each group. * p<0.05 compared to controls.</p>", "links"=>[], "tags"=>["anatomy", "Musculoskeletal system", "muscles", "cell biology", "Signal transduction", "cell signaling", "Signaling cascades", "Calcium signaling cascade", "Calcium signaling", "Calcium-mediated signal transduction", "Molecular cell biology", "organisms", "animals", "vertebrates", "mammals", "rodents", "rats", "physiology", "Muscle physiology", "Muscle biochemistry", "Muscle functions", "systems biology", "Integrative physiology", "health care", "physiotherapy", "Sports and exercise medicine", "Model organisms", "Animal models", "clenbuterol", "edl", "calpain"], "article_id"=>1086978, "categories"=>["Biological Sciences"], "users"=>["Pascal Sirvent", "Aymerick Douillard", "Olivier Galbes", "Christelle Ramonatxo", "Guillaume Py", "Robin Candau", "Alain Lacampagne"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100281.g005", "stats"=>{"downloads"=>2, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_chronic_clenbuterol_treatment_on_EDL_muscle_calpain_activity_/1086978", "title"=>"Effects of chronic clenbuterol treatment on EDL muscle calpain activity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-27 02:47:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/1570124"], "description"=>"<p><b>A,</b> Effects of clenbuterol (CLB) treatment for 21 days on EDL maximal isometric tension. Left graph, P<sub>0</sub>: maximal isometric tetanic tension, in mN; Right graph, sP<sub>0</sub> specific maximal isometric tetanic tension, in N/cm<sup>2</sup>. * p<0.05 compared to controls (CTR, untreated animals). <b>B,</b> Recordings show the decrease in tension resulting from the fatigue protocol in control EDL muscles (CTR) in which T<sub>lim</sub> was almost 50 s and in clenbuterol treated EDL muscles (CLB) in which T<sub>lim</sub> was about 34 s. Black dashed lines represent the maximal force and 50% of the initial force. The grey dashed line in the CLB panel represents 50% of the initial force of CTR for comparison. <b>C,</b> Mean ± SEM of the T<sub>lim</sub> values/group (n = 15 for CTR; n = 22 for CLB). * p<0.05 compared to CTL.</p>", "links"=>[], "tags"=>["anatomy", "Musculoskeletal system", "muscles", "cell biology", "Signal transduction", "cell signaling", "Signaling cascades", "Calcium signaling cascade", "Calcium signaling", "Calcium-mediated signal transduction", "Molecular cell biology", "organisms", "animals", "vertebrates", "mammals", "rodents", "rats", "physiology", "Muscle physiology", "Muscle biochemistry", "Muscle functions", "systems biology", "Integrative physiology", "health care", "physiotherapy", "Sports and exercise medicine", "Model organisms", "Animal models", "clenbuterol", "contractile"], "article_id"=>1086975, "categories"=>["Biological Sciences"], "users"=>["Pascal Sirvent", "Aymerick Douillard", "Olivier Galbes", "Christelle Ramonatxo", "Guillaume Py", "Robin Candau", "Alain Lacampagne"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100281.g002", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_chronic_clenbuterol_treatment_on_intact_muscle_contractile_properties_/1086975", "title"=>"Effects of chronic clenbuterol treatment on intact muscle contractile properties.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-27 02:47:00"}

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