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Previous studies on pulmonary arterial smooth muscle cells have shown that nicotinic acid adenine dinucleotide phosphate (NAADP) evokes highly localized intracellular Ca(2+) signals by mobilizing thapsigargin-insensitive stores. Such localized Ca(2+) signals may initiate global Ca(2+) waves and contraction of the myocytes through the recruitment of ryanodine receptors on the sarcoplasmic reticulum via Ca(2+)-induced Ca(2+) release. Here we show that NAADP evokes localized Ca(2+) signals by mobilizing a bafilomycin A1-sensitive, lysosome-related Ca(2+) store. These lysosomal stores facilitate this process by co-localizing with a portion of the sarcoplasmic reticulum expressing ryanodine receptors to comprise a highly specialized trigger zone for NAADP-dependent Ca(2+) signaling by the vasoconstrictor hormone, endothelin-1. These findings further advance our understanding of how the spatial organization of discrete, organellar Ca(2+) stores may underpin the generation of differential Ca(2+) signaling patterns by different Ca(2+)-mobilizing messengers.

Original publication




Journal article


J Biol Chem

Publication Date





54319 - 54326


Animals, Calcium, Endothelin-1, Enzyme Inhibitors, Inositol 1,4,5-Trisphosphate, Lysosomes, Macrolides, Male, Muscle, Smooth, Vascular, NADP, Pulmonary Artery, Rats, Rats, Wistar, Ryanodine, Ryanodine Receptor Calcium Release Channel, Sarcoplasmic Reticulum, Signal Transduction, Thapsigargin, Tight Junctions, Vacuolar Proton-Translocating ATPases