Effects of beta 2-agonist administration and exercise on contractile activation of skeletal muscle fibers

Lynch, Gordon S., Alan Hayes, Siun P. Campbell, and David A. Williams. Effects of₂-agonist administration andexercise on contractile activation of skeletal muscle fibers.J. Appl. Physiol. 81(4):1610-1618, 1996.Clenbuterol, a₂-adrenoceptor agonist, hastherapeutic potential for the treatment of muscle-wasting diseases, yetits effects, especially at the single-fiber level, have not been fullycharacterized. Male C57BL/10 mice were allocated to three groups:Control-Treated mice were administered clenbuterol (2 mg ^· kg^{1 ·} day¹)via their drinking water for 15 wk; Trained-Treated mice underwent low-intensity training (unweighted swimming, 5 days/wk, 1 h/day) inaddition to receiving clenbuterol; and Control mice were sedentary anduntreated. 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 ofTreated mice exhibited decreases inCa²⁺ sensitivity. Enduranceexercise offset clenbuterol's effects, demonstrated by similarCa²⁺ sensitivities in theTrained-Treated and Control groups. Long-term clenbuterol treatment didnot affect the normalized maximal tension of fast or slow fibers butincreased the proportion of fast fibers in the soleus muscle. Trainingincreased the proportion of fibers with high and intermediate succinatedehydrogenase activity in the EDL and soleus muscles, respectively. Ifclenbuterol is to be used for treating muscle-wasting disorders, someform of low-intensity exercise might be encouraged such thatpotentially deleterious slow-to-fast fiber type transformations areminimized. Indeed, in the mouse, low-intensity exercise appears toprevent these effects.