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An inverse relationship exists between striated muscle fiber size and its oxidative capacity. This relationship implies that muscle fibers, which are triggered to simultaneously increase their mass/strength (hypertrophy) and fatigue resistance (oxidative capacity), increase these properties (strength or fatigue resistance) to a lesser extent compared to fibers increasing either of these alone. Muscle fiber size and oxidative capacity are determined by the balance between myofibrillar protein synthesis, mitochondrial biosynthesis and degradation. New experimental data and an inventory of critical stimuli and state of activation of the signaling pathways involved in regulating contractile and metabolic protein turnover reveal: (1) higher capacity for protein synthesis in high compared to low oxidative fibers; (2) competition between signaling pathways for synthesis of myofibrillar proteins and proteins associated with oxidative metabolism; i.e., increased mitochondrial biogenesis via AMP-activated protein kinase attenuates the rate of protein synthesis; (3) relatively higher expression levels of E3-ligases and proteasome-mediated protein degradation in high oxidative fibers. These observations could explain the fiber type-fiber size paradox that despite the high capacity for protein synthesis in high oxidative fibers, these fibers remain relatively small. However, it remains challenging to understand the mechanisms by which contractile activity, mechanical loading, cellular energy status and cellular oxygen tension affect regulation of fiber size. Therefore, one needs to know the relative contribution of the signaling pathways to protein turnover in high and low oxidative fibers. The outcome and ideas presented are relevant to optimizing treatment and training in the fields of sports, cardiology, oncology, pulmonology and rehabilitation medicine. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate effects of albumin and insulin separately as well as in combination on mature muscle fibres during long-term culture. Single muscle fibres were dissected from m. iliofibularis of Xenopus laevis and attached to a force transducer in a culture chamber. Fibres were cultured in a serum-free medium at slack length (mean sarcomere length 2.3 μm) for 8 to 22 days. The medium was supplemented with (final concentrations): (1) bovine insulin (6 nmol/L or 200–600 nmol/L), (2) 0.2% bovine albumin or (3) 0.2% bovine albumin in combination with insulin (120 nmol/L). In culture medium with insulin, 50% of the muscle fibres became in-excitable within 7–12 days, whereas the other 50% were stable. Caffeine contractures of in-excitable muscle fibres produced 80.4 ± 2.4% of initial peak tetanic force, indicating impaired excitation–contraction (E–C) coupling in in-excitable fibres. In the presence of albumin, all cultured muscle fibres were stable for at least 10 days. Muscle fibres cultured in medium with insulin or albumin exclusively did not hypertrophy or change the number of sarcomeres in series. In contrast, muscle fibres cultured with both albumin and insulin showed an increase in tetanic force and fibre cross-sectional area of 19.6 ± 2.8% and 32.5 ± 4.9%, respectively, (means ± SEM.; P = 0.007) after 16.3 ± 1.7 days, whereas the number of sarcomeres in series remained unchanged. We conclude that albumin prevents muscle fibre damage and preserves E–C coupling in culture. Furthermore, albumin is important in regulating muscle fibre adaptation by a synergistic action with growth factors like insulin. [ABSTRACT FROM AUTHOR]

The aims of this study were (1) to determine the relationship between muscle fibre cross-sectional area and cytoplasmic density of myonuclei in high- and low-oxidative Xenopus muscle fibres and (2) to test whether insulin and long-term high fibre length caused an increase in the number of myonuclei and in the expression of α-skeletal actin and of myogenic regulatory factors (myogenin and MyoD) in these muscle fibres. In high- and low-oxidative muscle fibres from freshly frozen iliofibularis muscles, the number of myonuclei per millimetre fibre length was proportional to muscle fibre cross-sectional area. The in vivo myonuclear density thus seemed to be strictly regulated, suggesting that the induction of hypertrophy required the activation of satellite cells. The effects of muscle fibre length and insulin on myonuclear density and myonuclear mRNA content were investigated on high-oxidative single muscle fibres cultured for 4–5 days. Muscle fibres were kept at a low length (~15% below passive slack length) in culture medium with a high insulin concentration (~6 nmol/l: “high insulin medium”) or without insulin, and at a high length (~5% above passive slack length) in high insulin medium. High fibre length and high insulin medium did not change the myonuclear density of isolated muscle fibres during culture. High insulin increased the myonuclear α-skeletal actin mRNA content, whereas fibre length had no effect on α-skeletal actin mRNA content. After culture at high fibre length in high insulin medium, the myonuclear myogenin mRNA content was 2.5-fold higher than that of fibres cultured at low length in high insulin medium or in medium without insulin. Myonuclear MyoD mRNA content was not affected by fibre length or insulin. These in vitro experiments indicate that high muscle fibre length and insulin enhance muscle gene expression but that other critical factors are required to induce adaptation of muscle fibre size and performance. [ABSTRACT FROM AUTHOR]

This paper considers the literature and some new experimental results important for adaptation of muscle fiber cross-sectional area and serial sarcomere number. Two major points emerge: (1) general rules for the regulation of adaptation (for in vivo immobilization, low gravity conditions, synergist ablation, tenotomy and retinaculum trans-section experiments) cannot be derived. As a consequence, paradoxes are reported in the literature. Some paradoxes are resolved by considering the interaction between different levels of organization (e.g. muscle geometrical effects), but others cannot. (2) An inventory of signal transduction pathways affecting rates of muscle protein synthesis and/or degradation reveals controversy concerning the pathways and their relative contributions. A major explanation for the above is not only the inherently limited control of the experimental conditions in vivo, but also of in situ experiment s. Culturing of mature single Xenopus muscle fibers at high and low lengths (allowing longitudinal study of adaptation for periods up to 3 months) did not yield major changes in the fiber cross-sectional area or the serial sarcomere number. This is very different from substantial effects (within days) of immobilization in vivo. It is concluded that overall strain does not uniquely regulate muscle fiber size. Force transmission, via pathways other than the myotendinous junctions, may contribute to the discrepancies reported: because of substantial serial heterogeneity of sarcomere lengths within muscle fibers creating local variations in the mechanical stimuli for adaptation. For the single muscle fiber, mechanical signalling is quite different from the in vivo or in vitro condition. Removal of tensile and shear effects of neighboring tissues (even of antagonistic muscle) modifies or removes mechanical stimuli for adaptation. It is concluded that the study of adaptation of muscle size requires an integrative approach taking into account fundamental mechanisms of adaptation, as well as effects of higher levels of organization. More attention should be paid to adaptation of connective tissues within and surrounding the muscle and their effects on muscular properties. [ABSTRACT FROM AUTHOR]