Effects of beta 2-agonist administration and exercise on contractile activation of skeletal muscle fibers.
Clenbuterol, a beta 2-adrenoceptor agonist, has therapeutic potential for the treatment of muscle-wasting diseases, yet its effects, especially at the single-fiber level, have not been fully characterized. Male C57BL/10 mice were allocated to three groups: Control-Treated mice were administered clenbuterol (2 mg.kg-1. day-1) via their drinking water for 15 wk; Trained-Treated mice underwent low-intensity training (unweighted swimming, 5 days/wk, 1 h/day) in addition to receiving clenbuterol; and Control mice were sedentary and untreated. Contractile characteristics were determined on membrane-permeabilized fibers from the extensor digitorum longus (EDL) and soleus muscles. Fast fibers from the EDL and soleus muscles of Treated mice exhibited decreases in Ca2+ sensitivity. Endurance exercise offset clenbuterol's effects, demonstrated by similar Ca2+ sensitivities in the Trained-Treated and Control groups. Long-term clenbuterol treatment did not affect the normalized maximal tension of fast or slow fibers but increased the proportion of fast fibers in the soleus muscle. Training increased the proportion of fibers with high and intermediate succinate dehydrogenase activity in the EDL and soleus muscles, respectively. If clenbuterol is to be used for treating muscle-wasting disorders, some form of low-intensity exercise might be encouraged such that potentially deleterious slow-to-fast fiber type transformations are minimized. Indeed, in the mouse, low-intensity exercise appears to prevent these effects.
Department of Physiology, University of Melbourne, Parkville, Victoria, Australia. gslynch@umich.edu
G S
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Lynch
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Hayes
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Campbell
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Williams
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002976:Clenbuterol / Q000494:pharmacology*; D006651:Histocytochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology*; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010805:Physical Conditioning, Animal; D005082:Physical Exertion / Q000502:physiology*
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D002976:Clenbuterol