EXERCISE-INDUCED MUSCLE INJURY - A CALPAIN HYPOTHESIS

It is well established that periods of increased contractile activity result in significant changes in muscle structure and function. Such m orphological changes as sarcomeric Z-line disruption and sarcoplasmic reticulum vacuolization are characteristic of exercise-induced muscle injury. While the precise mechanism(s) underlying the perturbations to muscle following exercise remains to be elucidated, it is clear that disturbances in Ca2+ homeostasis and changes in the rate of protein de gradation occur. The resulting elevation in intracellular [Ca2+] activ ates the non-lysosomal cysteine protease, calpain. Because calpain cle aves a variety of protein substrates including cytoskeletal and myofib rillar proteins, calpain-mediated degradation is thought to contribute to the changes in muscle structure and function that occur immediatel y following exercise. In addition, calpain activation may trigger the adaptation response to muscle injury. The purpose of this paper is to: (i) review the chemistry of the calpain-calpastatin system; (ii) prov ide evidence for the involvement of the non-lysosomal, calcium-activat ed neutral protease (calpain) in the response of skeletal muscle prote in breakdown to exercise (calpain hypothesis); and (iii) describe the possible involvement of calpain in the inflammatory and regeneration r esponse to exercise.