4.7 Article

The alteration of calcium homeostasis in adult dystrophic mdx muscle fibers is worsened by a chronic exercise in vivo

期刊

NEUROBIOLOGY OF DISEASE
卷 17, 期 2, 页码 144-154

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2004.06.002

关键词

muscular dystrophy; calcium homeostasis; mechanical over-load; Mdx mouse; intact muscle fibers; in vivo exercise; mechanosensitive calcium channels; leak calcium channels; excitation-calcium release coupling; calcium imaging

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Chronic exercise in vivo aggravates dystrophy in mdx mice. Calcium homeostasis was evaluated ex vivo by micro-spectrofluorometry on tendon-to-tendon dissected extensor digitorum longus (EDL) muscle fibers. Resting cytosolic calcium ([Ca2+]i) and sarcolemmal permeability through Gd3+-sensitive mechanosensitive calcium (MsCa) channel were significantly higher in rods vs. wild-type fibers. The exercise further enhanced [Ca2+]i in mdx fibers and increased sarcolemmal permeability by activating nifedipine-sensitive leak calcium channels. The two genotypes did not differ in caffeine sensitivity and in the excitation-calcium release (ECaR) coupling mechanism by K, depolarization. The exercise produced a similar adaptation of activation curve of ECaR and of sensitivity to caffeine. However, the inactivation of ECaR of mdx fibers did not adapt to exercise. No fiber phenotype transition occurred in exercised muscle. We provide the first evidence that an in vivo exercise worsens the impaired calcium homeostasis of dystrophic fibers, supporting the role of enhanced calcium entrance in dystrophic progression. (C) 2004 Elsevier Inc. All rights reserved.

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