COORDINATE CHANGES OF MYOSIN LIGHT AND HEAVY-CHAIN ISOFORMS DURING FORCED FIBER-TYPE TRANSITIONS IN RABBIT MUSCLE

Skeletal muscle fibers are versatile entities, capable of changing the ir phenotype in response to altered functional demands. In the present study, fast-to-slow fiber type transitions were induced in rabbit tib ialis anterior (TA) muscles by chronic low-frequency stimulation (CLFS ). The time course of changes in relative protein concentrations of fa st and slow myosin light chain (MLC) isoforms and changes in their rel ative synthesis rates by in vivo labeling with [S-35]methionine were f ollowed during stimulation periods of up to 60 days. Generally, relati ve synthesis rates and protein concentrations changed in parallel; i.e ., fast isoforms decreased and slow isoforms increased. MLC3f, however , which turns over at a higher rate than the other light chains, exhib ited a conspicuous discrepancy between a markedly reduced relative syn thesis but only a moderate decrease in protein amount during the initi al 2 weeks of CLFS. Apparently, MLC3f is regulated independent of MLC1 f, with protein degradation playing an important role in its regulatio n. The exchange of fast MLC isoforms with their slow counterparts seem ed to correspond to the ultimate fast-to-slow (MHCIIa-->MHCl) transiti on at the MHC level. However, due to an earlier onset of the fast-to-s low transition of the regulatory light chain and the delayed fast-to-s low exchange of the alkali light chains, a spectrum of hybrid isomyosi ns composed of fast and slow light and heavy chains must have existed transiently in transforming fibers. Such hybrid isomyosins appeared to be restricted to MHCIIa- and MHCl-based combinations. In conclusion, fiber type specific programs that normally coordinate the expression o f myofibrillar protein isoforms seem to be maintained during fiber typ e transitions. Possible differences in post-transcriptional regulation may result in the transient accumulation of atypical combinations of fast and slow MIC and MHC isoforms, giving rise to the appearance of h ybrid fibers under the conditions of forced fiber type conversion. (C) 1996 Wiley-Liss, Inc.