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 Ca2+" the uptake of Ca2+ by mitochondria and the inositol 1,4,5-trisphosphate (IP3) cascade. These processes were recently found to be also present in skeletal muscle and are reviewed here. The "store-operated entry of Ca2+" 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 Ca2+ by mitochondria accelerates muscle relaxation and allows the adaptation of ATP supply to the increased energy demand. IP3 receptors are found in the nuclear envelope and are involved in Ca2+ waves propagating from one nucleus to another. This pathway is possibly involved in gene expression regulation. Finally, cytosolic Ca2+ buffers like parvalbumins modify [Ca2+](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 [Ca2+](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 Ca2+. How this increased entry of Ca2+ affects the local concentration of Ca2+ in subcellular compartments and whether this process is involved in the development of the disease are still unclear. (C) 2002 Elsevier Science B.V All rights reserved.