Rat soleus muscle was denervated for 3 or 7 days, and total membrane protein kinase C (PKC) activity and translocation and immunocytochemical localization of PKC isoforms were examined. Dietary administration of clenbuterol concomitant with denervation ameliorated the atrophic response and was associated with increased membrane PKC activity at both 3 (140%) and 7 (190%) days. Of the five PKC isoforms (α, ɛ, θ, ζ, and μ) detected in soleus muscle by Western immunoblotting, clenbuterol treatment affected only the PKC-α and PKC-θ forms. PKC-α was translocated to the membrane fraction upon denervation, and the presence of clenbuterol increased membrane-bound PKC-α and active PKC-α as assayed by Ser657 phosphorylation. PKC-θ protein was downregulated upon denervation, and treatment with clenbuterol further decreased both cytosolic and membrane levels. Immunolocalization of PKC-θ showed differences for regulatory and catalytic domains, with the latter showing fast-fiber type specificity. The results suggest potential roles of PKC-α and PKC-θ in the mechanism of action of clenbuterol in alleviating denervation-induced atrophy.
The type I insulin-like growth factor receptor mediates the rapid effects of multiplication-stimulating activity on membrane transport systems in rat soleus muscle.