Myonuclear domain in skeletal muscle fibers. A crit ical review.

The muscle cells, or myofibers, are one of the three multinucleated cell types, along with osteoclasts and cytotrophoblasts. This aspect of skeletal muscle has led to the concept of myonuclear domain, which is defined as the theoretical amount of cytoplasm within a muscle fiber controlled by a single myonucleus. Considering the huge plasticity of skeletal muscle fibers, the myonuclear domain has become one aspect of major interest under situations leading to muscle atrophy (spinal cord isolation and transaction, microgravity, hindlimb suspension and chronic denervation) hypertrophy (synergist ablation and bouts of exercise) and day-to-day wear and tear (age, body size, muscle function and fiber type-related differences). This concept is supported by several studies reporting that changes in muscle fibers’ cross-sectional area (CSA) are paralleled by an alteration in the number of myonuclei, maintaining constant the relationship between them. This implies a fairly strict regulation of the myonuclear number that is governed by two opposing mechanisms: the gain of myonuclei by the fusion of muscle stem cells into hypertrophying muscle fibers and the loss of myonuclei by apoptosis/necrosis in atrophying muscle fibers. The aim of this review is to scrutinize the changes in the myonuclear domain in skeletal muscle fibers considering the atrophic and hypertrophic processes, emphasizing the differences between the various methods utilized to achieve these morphological alterations, and the differences between muscle responses according to their phenotype (different function and fiber type composition) and animal age (relevance to sarcopenia).