title: Effect of clenbuterol on sarcoplasmic reticulum function in single skinned mammalian skeletal muscle fibers.
abstract: We examined the effect of the beta2-agonist clenbuterol (50 microM) on depolarization-induced force responses and sarcoplasmic reticulum (SR) function in muscle fibers of the rat (Rattus norvegicus; killed by halothane overdose) that had been mechanically skinned, rendering the beta2-agonist pathway inoperable. Clenbuterol decreased the peak of depolarization-induced force responses in the extensor digitorum longus (EDL) and soleus fibers to 77.2 +/- 9.0 and 55.6 +/- 5.4%, respectively, of controls. The soleus fibers did not recover. Clenbuterol significantly and reversibly reduced SR Ca2+ loading in EDL and soleus fibers to 81.5 +/- 2.8 and 78.7 +/- 4.0%, respectively, of controls. Clenbuterol also produced an approximately 25% increase in passive leak of Ca2+ from the SR of the EDL and soleus fibers. These results indicate that clenbuterol has direct effects on fast- and slow-twitch skeletal muscle, in the absence of the beta2-agonist pathway. The increased Ca2+ leak in the triad region may lead to excitation-contraction coupling damage in the soleus fibers and could also contribute to the anabolic effect of clenbuterol in vivo.
authors.affiliation: Department of Physiology, University of Western Australia, Nedlands 6907, Australia.
authors.forename: A J
authors.initials: AJ
authors.lastname: Bakker
authors.forename: S I
authors.initials: SI
authors.lastname: Head
authors.forename: A C
authors.initials: AC
authors.lastname: Wareham
authors.forename: D G
authors.initials: DG
authors.lastname: Stephenson
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002976:Clenbuterol / Q000494:pharmacology*; D004533:Egtazic Acid / Q000494:pharmacology; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000648:ultrastructure*; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000318:Adrenergic beta-Agonists; D002110:Caffeine; D004533:Egtazic Acid; D002118:Calcium; D002976:Clenbuterol