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Increased susceptibility to ATP via alteration of P2X receptor function in dystrophic mdx mouse muscle cells
Author(s) -
Yeung Davy,
Zabłocki Krzysztof,
Lien ChunFu,
Jiang Taiwen,
Arkle Stephen,
Brutkowski Wojciech,
Brown James,
Lochmuller Hanns,
Simon Joseph,
Barnard, Eric A.,
Górecki Dariusz C.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4022com
Subject(s) - myocyte , duchenne muscular dystrophy , extracellular , dystrophin , purinergic receptor , receptor , microbiology and biotechnology , mdx mouse , muscular dystrophy , biology , endocrinology , muscle disorder , myopathy , medicine , chemistry , biochemistry , genetics
Pathological cellular hallmarks of Duchenne muscular dystrophy (DMD) include, among others, abnormal calcium homeostasis. Changes in the expression of specific receptors for extracellular ATP in dystrophic muscle have been recently documented: here, we demonstrate that at the earliest, myoblast stage of developing dystrophic muscle a purinergic dystrophic phenotype arises. In myoblasts of a dystrophin‐negative muscle cell line established from the mdx mouse model of DMD but not in normal myoblasts, exposure to extracellular ATP triggered a strong increase in cytoplasmic Ca 2 + concentrations. Influx of extracellular Ca 2 + was stimulated by ATP and BzATP and inhibited by zinc, Coomassie Brilliant Blue‐G, and KN‐62, demonstrating activation of P2X7 receptors. Significant expression of P2X4 and P2X7 proteins was immunodetected in dystrophic myoblasts. Therefore, full‐length dystrophin appears, surprisingly, to play an important role in myoblasts in controlling responses to ATP. Our results suggest that altered function of P2X receptors may be an important contributor to pathogenic Ca 2 + entry in dystrophic mouse muscle and may have implications for the pathogenesis of muscular dystrophies. Treatments aiming at inhibition of specific ATP receptors could be of a potential therapeutic benefit.‐Yeung, D., Zabłocki, K., Lien, C.‐F., Jiang, T., Arkle, S., Brutkowski, W., Brown, J., Lochmuller, H., Simon, J., Barnard, E. A., Górecki, D. C. Increased susceptibility to ATP via alteration of P2X receptor function in dystrophic mdx mouse muscle cells. FASEB J. 20, 610–620 (2006)