Effect of protease inhibitors on skeletal muscle lysosomal enzyme activity and resting membrane potential

Inhibition of lysosomal enzyme activity by protease inhibitors in denervated muscle was studied in vitro by incubating muscle homogenates with increasing concentrations of inhibitor and determining acid protease activity. Pepstatin was the most potent inhibitor of protease activity, followed in order of inhibitor potency by chloroquine, aprotinin, and leupeptin. The in vivo uptake of chloroquine or leupeptin by denervated muscle was greater than that of innervated muscle, and repeated administration of the drug led to a decrease in muscle N-acetylglucosaminidase activity. Repeated administration of chloroquine had no effect on resting membrane potential of muscle fibers in the soleus or extensor digitorum longus measured in vivo. Chloroquine attenuated the marked decrease in the resting membrane potential of the extensor 2.5 days after denervation, but had no effect on that of the denervated soleus. Possible involvement of proteases in lowering the membrane potential of denervated muscle is discussed.