Abnormal expression of glycogen phosphorylase genes in regenerated muscle.

Physiological and molecular biological properties of free, orthotopic grafts of rat extensor digitorum longus (EDL) muscle were determined at 28-, 42-, and 76-days postgraft. cDNA probes for the rat fetal (B), liver (L), and muscle (M) isozymes of glycogen phosphorylase were used to assay isozyme mRNA levels. Regenerating muscle grafts did not express nonmuscle phosphorylase isozymes in vivo in contrast to primary rat skeletal muscle explants in vitro. Low levels of M-phosphorylase mRNA were present at all stages of regeneration in the grafts. However, M-phosphorylase mRNA levels and activity increased markedly and nonuniformly in a subset of functionally and morphologically stabilized regenerated muscle fibers between 42- and 76-days postgraft. Biochemical, physiological, and histochemical characterization of the stabilized grafts demonstrated that all fibers present were innervated and indicated that innervation might be a necessary, but not sufficient, condition for the increase in M-phosphorylase expression. The nonuniform appearance of phosphorylase activity suggests that a differential activity profile imposed on muscle fibers by their motoneuron may govern M-phosphorylase gene expression.