Contractile properties of mice deficient in dystrophin and the NADPH subunit p47phox

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Duchenne muscular dystrophy is associated with a mutation in the gene encoding dystrophin. Dystrophin‐deficient muscle is highly susceptible to contraction‐induced injury. A report by N.P. Whitehead et al (2010) regarding mdx mice, described the efficacy of pharmacological inhibition of NADPH oxidase at decreasing contraction‐induced force deficits. This indicated that during lengthening contractions, NADPH oxidase may be a source of reactive oxygen species which contributes to the opening of stretch activated channels and the deleterious influx of extracellular calcium. To evaluate this proposal further and the role of p47phox – a subunit of NADPH oxidase – in particular, we tested the hypothesis that a stretch activated channel inhibitor (streptomycin), antioxidant (N‐acetylcysteine), calcium‐free buffer, and p47phox deficiency would decrease contraction‐induced injury for muscles of mdx mice. Mdx mice were crossed with p47phox null mice and isolated extensor digitorum longus muscles were exposed to the various conditions. Specific force was unaffected in all cases. Force deficits were reduced with the addition of streptomycin, N‐aceytcysteine, or calcium‐free buffer confirming earlier reports. A deficiency in p47phox diminished the increased muscle mass typical of mdx mice. However, lacking p47phox had no effect on force deficit. The results are consistent with reactive oxygen species and the influx of extracellular calcium via stretch activated channels mediating contraction‐induced injury in dystrophin deficient muscle. However, the findings indicate that the absence of p47phox does not reduce muscle dysfunction associated with dystrophin deficiency.