J.B. Wolffe memorial lecture. Activity-induced fast to slow transitions in mammalian muscle.

Chronically increased contractile activity by low-frequency stimulation induces a transformation of fast- into slow-twitch muscle fibers in the rabbit. This transformation is progressive with the duration of the stimulation and affects various functional systems of the muscle fiber in an orderly sequence. Early changes in enzyme activities and isozymes of energy metabolism result in a "white to red" metabolic transformation. Simultaneously, cytosolic Ca2+-binding and Ca2+-sequestration are reduced by a decrease in parvalbumin and a transformation of the sarcoplasmic reticulum membranes. The fast to slow transformation is completed by an exchange of fast with slow-type myosin isoforms. Changes in total RNA and qualitative and quantitative alterations in translatable mRNA indicate that the various transitions result from altered translational and transcriptional activities. The qualitative similarity of changes evoked by long-term endurance training suggest that fast to slow transitions represent a regular response to increased contractile activity. The specific time courses at which various functional systems of the fiber respond, point to the existence of different thresholds. These differences increase the adaptability of the fiber by changing its properties in a graded fashion. The phenotype of a muscle fiber appears thus to be dynamic and is modified according to the actual functional demand.