Induction of a fast-oxidative phenotype by chronic muscle stimulation: mechanical and biochemical studies

Abstract

We studied changes in the mechanical properties and myosin isoform composition of rabbit tibialis anterior muscles that were subjected to continuous stimulation at 2.5 Hz for up to 12 wk. The effects of stimulation at 2.5 Hz were less profound than those observed for the same duration of stimulation at 10 Hz (12). Stimulation at 10 Hz for 12 wk induced complete transformation to a slow-contracting muscle homogeneous in slow myosin isoforms; stimulation for the same period at 2.5 Hz resulted in moderate changes in contractile speed and a very small increase in the synthesis of slow myosin isoforms. On the other hand, the fatigue resistance of muscles stimulated at 2.5 Hz was as great, in both isometric and dynamic fatigue tests, as that of the muscles stimulated at 10 Hz. Thus entire fast skeletal muscles can be transformed to a state in which fast myosin isoforms continue to be synthesized, but the oxidative capacity is sufficient to support sustained working at a higher power output than that associated with slow muscle.

The dose-related response of rabbit fast muscle to long-term low-frequency stimulation

“…Little difference was seen between the properties of muscles stimulated for 10 months in this study and those of muscles stimulated at the same frequency for 12 weeks. 19 The longer period of stimulation did not produce additional slowing; if anything, the isometric contraction and half-relaxation times were slightly shorter, possibly because of an increase in the stiffness of series elastic elements. The stability of properties over this prolonged period argues against a continuing low rate of transformation, and again supports the notion of a threshold for change.…”

“…30,34,38 A more recent finding is that lower frequencies of stimulation produce an intermediate state of conversion: stimulation at 2.5 Hz for 12 weeks resulted in a muscle consisting mainly of type 2A fibers. 19,27 These observations were foreshadowed to some extent by work in which a lower aggregate amount of stimulation had been delivered by altering the daily duration rather than the frequency of stimulation. over a period of 7 weeks.…”

“…In fact it is difficult to imagine that the muscles in this study were in anything other than a stable condition, because their properties had not departed substantially from those already established by 12 weeks of stimulation. 19,27 The fact remains that the incidence of fibers with dual expression was greater in rabbit muscles that had been stimulated for 10 months than in the corresponding unstimulated controls.…”

“…5,38 However, stimulation at the lower frequency of 2.5 Hz for 12 weeks produces an intermediate state of transformation in which myosin is present mainly as the fast, type 2A isoform. 19 This finding offers the prospect of a new approach in which the properties of the muscle are engineered to combine speed and power of contraction with the necessary resistance to fatigue.…”

Cardiac assistance from skeletal muscle: a reappraisal☆

“…This was a misconception. Fatigue resistance depends on energy metabolism, which can be changed with a stimulation régime that does not induce slow myosin expression [40][41][42][43][44]. The resultant muscle has a '2A' phenotype, with the necessary fatigue resistance allied to fast contractile characteristics.…”