AuPS Logo Programme
Previous Next PDF

Role of mechanosensitive channels in skeletal muscle damage and muscular dystrophy

D.G. Allen, Physiology, University of Sydney, Camperdown, NSW, Australia

Muscles which are stretched during contraction are liable to a mild form of muscle damage including immediate weakness and delayed stiffness, soreness and swelling. In muscular dystrophy, which is characterized by profound muscle degeneration, stretch-induced damage is more severe and recovery incomplete. We have studied the mechanisms involved by measuring ionic changes in single fibres following a short series of stretched contractions. Intracellular sodium shows a slow increase after stretched contractions, not seen after isometric contractions, which can be prevented by either Gd3+ or streptomycin (Yeung et al., 2003) . Both Gd3+ and streptomycin block a class of mechanosensitive channels (MSCs), permeable to both Na+ and K+>, present in mammalian muscle fibres (Franco-Obregon & Lansman, 2002) . In mdx mice, which lack dystrophin, muscles showed an increased resting [Na+]i and a greater increase in [Na+]i following stretched contractions which was also blocked by the above agents. We have previously shown that stretched contraction increase resting [Ca2+]i but reduced tetanic [Ca2+]i (Balnave & Allen, 1995) . Recently we found that Gd3+, streptomycin or a potent blocker of MSCs, GsMTx4, could prevent the rise in resting [Ca2+]i and simultaneously increased the tetanic [Ca2+]i from the reduced level observed after stretched contractions. In both wild-type and mdx muscles the reduced force following stretched contractions was partly reversed by MSC blockers, presumably as a consequence of the increased tetanic [Ca2+]i noted above.

These data suggest that MSCs are present in both wild-type and mdx muscle and are persistently opened by stretched contractions. The subsequent entry of Na+ and Ca2+ may have roles in the reduced force and perhaps other aspects of muscle damage.

(1) Balnave CD & Allen DG (1995). Intracellular calcium and force in single mouse muscle fibres following repeated contractions with stretch. J Physiol 488, 25-36.

(2) Franco-Obregon A & Lansman JB (2002). Changes in mechanosensitive channel activity following mechanical stimulation in skeletal muscle myotubes from the mdx mouse. J Physiol 539, 391-407.

(3) Yeung EW, Head SI & Allen DG (2003). Gadolinium reduces short-term stretch-induced muscle damage in isolated mdx mouse muscle fibres. J Physiol 552, 449-458.