Specification of Myofibers

The proper specification of myofibers is essential for body movement, endurance, and metabolic regulation. Myofibers adopt their specific contractile and metabolic properties depending upon the pattern of excitation by motor neurons. These properties are best illustrated by the classical cross-innervation studies where reinnervation of slow-oxidative muscle by motor neurons normally innervating fast-glycolytic fibers are able to induce a slow-oxidative to fast-glycolytic change (Buller et al. 1960). Motor neurons that stimulate myofibers at tonic, low frequencies (10-20 Hz) result in a slow-oxidative phenotype, while those stimulating myofibers at phasic, high frequencies (100-150 Hz) results in a fast-glycolytic phenotype (Chin and Allen 1996; Hennig and Lomo 1985). Thus, the innervating motor neuron determines the pattern of excitation and thus myofiber type.

Importantly, the adult myofiber phenotype is not permanent. The size, contractility, and metabolic properties of myofibers can all undergo changes or remodeling [reviewed in Bassel-Duby and Olson (2006)]. For example, reduced neuromuscular activity caused by inactivity, aging or neuromuscular disease can lead to reduction in muscle size, termed atrophy. Inactivity also causes an increase in fast-glycolytic fibers. Conversely, repetitive use such as aerobic exercise induces muscle hypertrophy and a concomitant increase in slow-oxidative fibers. This plasticity, which is central to the physiological adaptation, is necessary for skeletal muscle to meet changing functional demands and perform different tasks. On the other hand, the pathological remodeling of skeletal muscle could lead to serious health problems, such as a loss of muscle mass, termed muscle atrophy (Fig. 1).

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