In this study, we have tested the hypothesis that augmented [Ca(2+)] in subcellular regions or organelles, which are known to play a key role in cell survival, is the missing link between Ca(2+) homeostasis alterations and muscular degeneration associated with muscular dystrophy. To this end, different targeted chimeras of the Ca(2+)-sensitive photoprotein aequorin have been transiently expressed in subcellular compartments of skeletal myotubes of mdx mice, the animal model of Duchenne muscular dystrophy. Direct measurements of the [Ca(2+)] in the sarcoplasmic reticulum, [Ca(2+)](sr), show a higher steady state level at rest and a larger drop after KCl-induced depolarization in mdx compared with control myotubes. The peaks in [Ca(2+)] occurring in the mitochondrial matrix of mdx myotubes are significantly larger than in controls upon KCl-induced depolarization or caffeine application. The augmented response of mitochondria precedes the alterations in the Ca(2+) responses of the cytosol and of the cytoplasmic region beneath the membrane, which become significant only at a later stage of myotube differentiation. Taking into account the key role played by mitochondria Ca(2+) handling in the control of cell death, our data suggest that mitochondria are potential targets of impaired Ca(2+) homeostasis in muscular dystrophy.
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|Titolo:||Alteration in calcium handling at the subcellular level in mdx myotubes.|
|Rivista:||THE JOURNAL OF BIOLOGICAL CHEMISTRY|
|Citazione:||V., R., M. L., M., V., T., R., M., M., C., Sorrentino, V., et al. (2001). Alteration in calcium handling at the subcellular level in mdx myotubes. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 276, 4647-4651.|
|Appare nelle tipologie:||1.1 Articolo in rivista|