Pharmacological control of cellular calcium handling in dystrophic skeletal muscle

• Published in: Neuromuscular disorders : NMD 2002-10, Vol.12, p.S155-S161
• Main Authors: Ruegg, Urs T, Nicolas-Métral, Valérie, Challet, Corinne, Bernard-Hélary, Katy, Dorchies, Olivier M, Wagner, Stéphanie, Buetler, Timo M
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Calcium - metabolism; Calcium Channels - drug effects; Calcium handling; Creatine; Creatine - pharmacology; Cytoplasm - metabolism; Duchenne muscular dystrophy; Dystrophin - deficiency; Dystrophin-dystroglycan complex; Glucocorticoids - pharmacology; Methylprednisolone - pharmacology; Mice; Mice, Inbred mdx; Mitochondria; Mitochondria - metabolism; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscular Dystrophy, Animal - drug therapy; Muscular Dystrophy, Animal - metabolism; Muscular Dystrophy, Duchenne - metabolism; Necrosis; Signal transduction; Signal Transduction - drug effects
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/S0960-8966(02)00095-0

Duchenne muscular dystrophy arises due to the lack of the cytoskeletal protein dystrophin. In Duchenne muscular dystrophy muscle, the lack of dystrophin is accompanied by alterations in the dystrophin–glycoprotein complex. We and others have found that the absence of dystrophin in cells of the Duchenne muscular dystrophy animal model, the mdx mouse, leads to elevated Ca 2+ influx and cytosolic Ca 2+ concentrations when exposed to stress. We have also shown that α-methylprednisolone, the only drug used successfully in the therapy of Duchenne muscular dystrophy, and creatine lowered cytosolic Ca 2+ levels in mdx myotubes. It is likely that chronic elevation of [Ca 2+] in the cytosol in response to stress is an initiating event for apoptosis and/or necrosis in Duchenne muscular dystrophy or mdx muscle and that alterations in mitochondrial function and metabolism are involved. Other cellular signalling pathways (e.g. nitric oxide) might also be affected.