title: Plasticity of human skeletal muscle: gene expression to in vivo function.
abstract: Human skeletal muscle is a highly heterogeneous tissue, able to adapt to the different challenges that may be placed upon it. When overloaded, a muscle adapts by increasing its size and strength through satellite-cell-mediated mechanisms, whereby protein synthesis is increased and new nuclei are added to maintain the myonuclear domain. This process is regulated by an array of mechanical, hormonal and nutritional signals. Growth factors, such as insulin-like growth factor I (IGF-I) and testosterone, are potent anabolic agents, whilst myostatin acts as a negative regulator of muscle mass. Insulin-like growth factor I is unique in being able to stimulate both the proliferation and the differentiation of satellite cells and works as part of an important local repair and adaptive mechanism. Speed of movement, as characterized by maximal velocity of shortening (V(max)), is regulated primarily by the isoform of myosin heavy chain (MHC) contained within a muscle fibre. Human fibres can express three MHCs: MHC-I, -IIa and -IIx, in order of increasing V(max) and maximal power output. Training studies suggest that there is a subtle interplay between the MHC-IIa and -IIx isoforms, with the latter being downregulated by activity and upregulated by inactivity. However, switching between the two main isoforms appears to require significant challenges to a muscle. Upregulation of fast gene programs is caused by prolonged disuse, whilst upregulation of slow gene programs appears to require significant and prolonged activity. The potential mechanisms by which alterations in muscle composition are mediated are discussed. The implications in terms of contractile function of altering muscle phenotype are discussed from the single fibre to the whole muscle level.
authors.affiliation: Division of Applied Biomedical Research, School of Biomedical & Health Sciences, King's College London, 4.14 Shepherd's House, Guy's Campus, London SE1 1UL, UK. s.harridge@kcl.ac.uk
authors.forename: Stephen D R
authors.initials: SD
authors.lastname: Harridge
mesh_terms: D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D009119:Muscle Contraction / Q000235:genetics*; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*