Gadolinium reduces short-term stretch-induced muscle damage in isolated mdx mouse muscle fibres

Abstract

Duchenne muscular dystrophy is a lethal muscle disease caused by absence of the protein dystrophin which is part of a glycoprotein complex located on the intracellular surface of the surface membrane. The precise function of dystrophin and the reason why its absence causes severe muscle damage are unclear. Stretch-induced muscle damage is well recognised in normal muscle and is more severe in muscles from animals lacking dystrophin (mdx mice). It has been proposed that stretch-induced damage underlies the progression of damage in muscular dystrophy. In the present study we confirm that single fibres from mdx muscle are more susceptible to stretch-induced damage and show that there is an associated rise in intracellular sodium concentration ([Na+]i) which is greater than in wild-type mice. We show that this rise in [Na+]i can be prevented by Gd3+, which is an established blocker of stretch-activated channels. mdx fibres have a higher than normal resting [Na+]i and this is also reduced by Gd3+. If Gd3+ is applied over the period in which [Na+]i rises following stretched contraction, it prevents one component of the reduced force. The other component of reduced force is caused by inhomogeneity of sarcomeres and can be minimised by stretching the muscle to its new optimum length. These experiments show that part of the short-term damage caused by stretch in mdx fibres can be prevented by blocking stretch-activated channels.