Duchenne Muscular dystrophy is an inherited disease caused by the absence of dystrophin. a structural protein normally located under the sarcolemma of skeletal muscle fibers Muscle degeneration occuring in this disease is thought to be partly caused by increased Ca2+ entry through sarcolemmal cationic channels. Using the Mn2+ quench method. we show here that Mn2+ entry triggered by Ca2+ store depletion but not basal Mn2+ entry relies on Ca2+-independent PLA(2) (iPLA(2)) activity in dystrophic fibers isolated from a murine model of Duchenne muscular dystrophy. the mdx(5cv) mouse iPLA(2) was found to be localized in the vicinity of the sarcolemma and consistently. the iPLA(2) lipid product lysophosphatidylcholine was found to trigger Ca2+ entry through sarcolemmal channels. suggesting that it acts as an intracellular messenger responsible for store-operated channels opening in dystrophic fibers Our results Suggest that inhibition of iPLA(2) and lysophospholipid production may be of interest to reduce Ca2+ entry and Subsequent degeneration of dystrophic muscle (C) 2009 Elsevier Inc All rights reserved