Effect of clenbuterol on sarcoplasmic reticulum function in single skinned mammalian skeletal muscle fibers

1 Department of Physiology, University of Western Australia, Nedlands 6907; 2 School of Physiology and Pharmacology, University of New South Wales, Sydney 2052; 4 School of Zoology, La Trobe University, Bundoora 3083, Australia; and 3 Division of Neuroscience, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom We examined the effect of the 2 -agonist clenbuterol (50 µM) 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 2 -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 Ca 2+ loading in EDL and soleus fibers to 81.5 ± 2.8 and 78.7 ± 4.0%, respectively, of controls. Clenbuterol also produced an ~25% increase in passive leak of Ca 2+ 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 2 -agonist pathway. The increased Ca 2+ 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. calcium uptake; calcium leak; calcium release; -agonist; excitation-contraction coupling; anabolism