The plasticity of human skeletal muscle: From gene expression to in vivo functio

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Exp Physiol. 2007 Jul 13

Translational Review:The plasticity of human skeletal muscle: From

gene expression to in vivo function.

Harridge SD.

King's College London.

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.