Localized expression of specific P2X receptors in dystrophin-deficient DMD and mdx muscle

Using a combination of molecular and immunohistochemical methods, we have obtained evidence for a distinctive change in the expression patterns of ATP-gated (P2X) receptor subunits in dystrophic muscle from both Duchenne muscular dystrophy (DMD) patients and the mdx mouse model. In control myofibres there was no staining for any P2X subtype studied here, although P2X1 stained the smooth muscle of the blood vessels and P2X6 nerves and the tunica intima in small arteries. In contrast, P2X1 and P2X6 were co-expressed strongly in small regenerating muscle fibres in the dystrophic muscles, whereas this expression decreased in fully regenerated fibres. Moreover, immunoreactivity for the P2X2 receptor re-appeared in dystrophic muscle, where it co-localised with the Type 1 fibres. There is, thus, a burst of production of several P2X receptor subtypes in regenerating dystrophic muscle, which may have implications for drug targets for this muscle pathology.