Received March 28, 2007
Revised May 11, 2007
Accepted after revision July 3, 2007

¹ King's College London

^* To whom correspondence should be addressed. E-mail: s.harridge{at}kcl.ac.uk.

	Abstract

Human skeletal muscle is a highly heterogeneous tissue being 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 negative regulator of muscle mass. IGF-I is particularly unique in being able to stimulate both the proliferation and differentiation of satellite cells and works as part of an important local repair and adaptive mechanism. Speed of movement, as characterised by maximum velocity of shortening (Vmax), is regulated primarily by the isoform of myosin heavy chain (MHC) contained within a muscle fibre. Human fibres can express three MHC; with increasing Vmax and maximum power output (MHC-I, IIa and IIx). Training studies suggest that there is a subtle interplay between the MHC-IIa and MHX-IIx isoforms with the latter being down regulated 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.

Key Words: Exercise, Muscle, Plasticity