Alteration in calcium handling at the subcellular level in mdx myotubes |
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Authors: | Robert V Massimino M L Tosello V Marsault R Cantini M Sorrentino V Pozzan T |
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Institution: | Department of Biomedical Sciences, CNR Center of Biomembranes, University of Padova, 35131 Padua, Italy. |
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Abstract: | 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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