New aspects of calcium signaling in skeletal muscle cells: implications in Duchenne muscular dystrophy.
Calcium is the most ubiquitous second messenger. Its concentration inside the cell is tightly regulated by a series of mechanisms, among which some have been extensively studied in nonmuscle cells. This is the case of the "store-operated entry of Ca(2+)", the uptake of Ca(2+) by mitochondria and the inositol 1,4,5-trisphosphate (IP(3)) cascade. These processes were recently found to be also present in skeletal muscle and are reviewed here. The "store-operated entry of Ca(2+)" allows the refilling of the stores after muscle fiber depolarization and is activated even after a partial depletion of the sarcoplasmic reticulum (SR). The uptake of Ca(2+) by mitochondria accelerates muscle relaxation and allows the adaptation of ATP supply to the increased energy demand. IP(3) receptors are found in the nuclear envelope and are involved in Ca(2+) waves propagating from one nucleus to another. This pathway is possibly involved in gene expression regulation. Finally, cytosolic Ca(2+) buffers like parvalbumins modify [Ca(2+)](i) transients and, therefore, muscle mechanics. The importance of these regulation mechanisms is also evaluated in Duchenne muscular dystrophy (DMD), a disease in which impairment of [Ca(2+)](i) homeostasis has been postulated but remains, however, controversial. This genetic disease is indeed characterized by the absence of a cytoskeletal protein called dystrophin, a situation leading to a disorganization of the cytoskeleton and to an abnormal influx of Ca(2+). How this increased entry of Ca(2+) affects the local concentration of Ca(2+) in subcellular compartments and whether this process is involved in the development of the disease are still unclear.
Gailly
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Département de Physiologie et de Pharmacologie, Université catholique de Louvain, Av. Hippocrate 55/40, 1200, Brussels, Belgium. gailly@fymu.ucl.ac.be
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D020388:Muscular Dystrophy, Duchenne / Q000209:etiology*; D010320:Parvalbumins / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D015220:Calcium Channels; D010320:Parvalbumins; D002118:Calcium