EFFECTS OF BETA(2)-AGONIST ADMINISTRATION AND EXERCISE ON CONTRACTILEACTIVATION OF SKELETAL-MUSCLE FIBERS

Clenbuterol, a beta(2)-adrenoceptor agonist, has therapeutic potential for the treatment of muscle-wasting diseases, yet its effects, especi ally at the single-fiber level, have not been fully characterized. Mal e C57BL/10 mice were allocated to three groups: Control-Treated mice w ere administered clenbuterol (2 mg . kg(-1). day(-1)) via their drinki ng water for 15 wk; Trained-Treated mice underwent low-intensity train ing (unweighted swimming, 5 days/wk, 1 h/day) in addition to receiving clenbuterol; and Control mice were sedentary and untreated. Contracti le characteristics were determined on membrane-permeabilized fibers fr om the extensor digitorum longus (EDL) and soleus muscles. Fast fibers from the EDL and soleus muscles of Treated mice exhibited decreases i n Ca2+ sensitivity. Endurance exercise offset clenbuterol's effects, d emonstrated by similar Ca2+ sensitivities in the Trained-Treated and C ontrol groups. Long-term clenbuterol treatment did not affect the norm alized maximal tension of fast or slow fibers but increased the propor tion of fast fibers in the soleus muscle. Training increased the propo rtion of fibers with high and intermediate succinate dehydrogenase act ivity in the EDL and soleus muscles, respectively. If clenbuterol is t o be used for treating muscle-wasting disorders, some form of low-inte nsity exercise might be encouraged such that potentially deleterious s low-to-fast fiber type transformations are minimized. Indeed, in the m ouse, low-intensity exercise appears to prevent these effects.