Changes in Myosin Heavy Chain Isoforms During Chronic Low-frequency Stimulation of Rat Fast Hindlimb Muscles. A Single-fiber Study

Fast-twitch rat muscles contain three fast myosin heavy chains (HC) which can be separated by density gradient gel electrophoresis. Their mobility increases in the order of HCIIa less than HCIId less than HCIIb. In contrast to the rabbit, where chronic low-frequency nerve stimulation induces a fast-to-slow conversion, stimulation for up to 56 days does not lead to appreciable increases in the relative concentration of the slow myosin heavy chain HCI in rat fast-twitch muscles. However, chronic stimulation of rat fast-twitch muscle does evoke a rearrangement of the fast myosin heavy chain isoform pattern with a progressive decrease in HCIIb and progressive increases in HCIIa and HCIId. As judged from the time course and extent of these transitions, it appears that HCIId is an intermediate form between HCIIb and HCIIa. Single-fiber analyses of normal muscles make it possible to assign these heavy chain isoforms to histochemically defined fiber types IIB, IID, and IIA. The stimulation-induced fiber transformations produce numerous hybrid fibers displaying more than one myosin heavy chain isoform. Some transforming fibers contain up to four different myosin heavy chain isoforms.