Streptomycin reduces stretch-induced membrane permeability in muscles from mdx mice

It is well-known that muscles from mdx mice are more susceptible to membrane damage from eccentric contractions than wildtype muscles. The present study tested the hypothesis that the stretch-induced membrane permeability in dystrophic muscle is due to Ca2+ entry through stretch-activated channels (SACs) and the subsequent activation of Ca2+-dependent degradative pathways. Eccentric contractions were carried out on muscles from mdx and wild-type mice, both on isolated muscles and on intact mice subjected to downhill running on a treadmill. In isolated muscles the SAC blockers, streptomycin and GsMTx4, improved force and significantly reduced the uptake of procion orange dye into fibres from mdx muscles, which increased progressively over 60 min after the eccentric contractions. In experiments on intact mdx mice, streptomycin also partially prevented the reduced force and the increased membrane permeability (Evans Blue Dye uptake). The results suggest that Ca2+ entry through SACs activates Ca2+-dependent pathways, which are the main cause of the increased membrane permeability in mdx muscle. (C) 2006 Elsevier B.V. All rights reserved.