Fast-to-slow transition in myosin heavy chain expression of rabbit muscle fibres induced by chronic low-frequency stimulation.

An in situ-hybridization assay using a digoxigenin-labeled cRNA probe specific for the slow myosin heavy chain (HCI) was established. Type I fibres of normal rabbit muscles were stained with this probe. The reaction product was confined to the perinuclear regions of the subsarcolemmal space and extended along the I-bands into the fibre core region. Myosin HCI mRNA was also detected in transforming fibres of low-frequency stimulated rabbit fast-twitch muscles. Its intracellular distribution resembled that of normal type I fibres, but higher amounts of the message were present in fibres undergoing a fast-to-slow transition. The number of HCI mRNA-positive fibres in stimulated muscles increased in a time-dependent manner and correlated with the amount of myosin HCI protein in these muscles. These findings support the notion that enhanced transcription of the slow myosin HC gene leads to an increased translation of HCI mRNA during the stimulation-induced fibre transformation. Finally, the progressive increase in fibres expressing myosin HCI mRNA indicates that the fast-to-slow fibre conversion occurs in a sequential manner. The pre-existing type IIA fibres appear to transform first, whereas fibre types IIB and IID have to first reach the IIA state. Adult muscle fibers represent versatile entities and may be transformed in response to altered functional demands. Although the majority of normal muscle fibers express only a single myosin HC isoform (for review see Pette and Staron, 1990), the coexistence of two or more myosin HC isoforms has been shown in transforming adult muscle fibers (Staron, Gohlsch, Pette, 1987; Termin, Staron, Pette, 1989).(ABSTRACT TRUNCATED AT 250 WORDS)