Selective gene expression during adaptation of muscle in response to different physiological demands.

Muscle is a very adaptable tissue in which gene expression is to a large extent influenced by physical signals. Adaptation to a different work regime is brought about by changes in fibre type and fibre cross-sectional area. We have shown both mass and phenotype are markedly altered by stretch and force production within a period as short as 4 days. This is associated with quantitative as well as qualitative changes in gene expression. The latter involves the expression of myosin heavy chain isogenes which encode different types of molecular motors. Some species of fish have exploited this and they are able to rebuild their myofibrillar systems for warm and cold temperature swimming by selective myosin gene expression. To understand how the different myosin isoform confer different contractile properties methods have been developed for cloning, sequencing and visualizing the structure of the ATPase site to explain how the molecular motors are designed. With regard to the chemical link between the physical signal and the upregulation of certain muscle genes we have cloned a new growth factor that is only expressed in muscles subjected to stretch and/or exercise and which is designed for autocrine/paracrine action. Experiments indicate that the expression of a local growth factor which induces repair, remodelling and hypertrophy is one of the ways cells respond to mechanical strain.