Altered gene expression in fast-twitch muscle induced by chronic low-frequency stimulation.

Increased neuromuscular activity via chronic low-frequency stimulation induces multiple fast-to-slow transitions in phenotypic properties that ultimately lead to fiber type conversions in the fast-twitch muscle of small mammals. Most of these alterations occur in an ordered sequence and result from the sequentially altered expression of myofibrillar and other protein isoforms. These changes relate to altered levels of specific mRNAs, followed by alterations in protein synthesis. As shown by the exchange of myosin heavy chain isoforms, protein degradation may be an additional control factor involved in the rearrangement of the myofibrillar apparatus. The degree of the various fast-to-slow transitions is species dependent and may be related to differences in thyroid hormone levels. It is suggested that the drastically and persistently depressed phosphorylation potential of the ATP system possibly serves to trigger the transformation process.