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Characterization of NAADP‐Induced Global and Local Calcium Signals in Rat Pulmonary Arterial Smooth Muscle Cells
Author(s) -
Jiang Yong-Liang,
Lin Amanda H.Y.,
Lee Suengwon,
Xia Yang,
Sham James S.K.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.871.3
Subject(s) - ryanodine receptor , thapsigargin , bafilomycin , extracellular , receptor , chemistry , ruthenium red , calcium signaling , biophysics , calcium , voltage dependent calcium channel , biochemistry , microbiology and biotechnology , biology , apoptosis , organic chemistry , autophagy
Ca 2+ signaling in vascular smooth muscle cells involves global and local interactions between multiple Ca 2+ influx and release pathways. Ca 2+ release pathways include IP 3 receptor‐, ryanodine receptor‐, and nicotinic acid adenine dinucleotide phosphate (NAADP) receptor‐mediated mechanisms. Recent studies demonstrated that the two‐pore channels (TPC1 and TPC2) are NAADP receptors located in the endo‐/lysosomes. Here we characterized the NAADP‐mediated Ca 2+ signals in rat pulmonary arterial smooth muscle cells (PASMCs). Application of the membrane permeable NAADP‐AM (0.25–1 μM) to PASMCs elicited concentration‐dependent increase in global [Ca 2+ ] i . It was blocked by the NAADP antagonist NED‐19 or the acidic vacuolar H + ‐ATPase bafilomycin A, suggesting Ca 2+ release from the lysosomal Ca 2+ stores. The Ca 2+ response was independent of extracellular Ca 2+ influx, and was unaffected by the IP 3 receptor blocker xestospongin C; but was partially inhibited by ryanodine or thapsigargin. Moreover, NAADP caused dramatic increase in local Ca 2+ release events, which was inhibited by ryanodine or NED‐19. The temporal and spatial properties of the NAADP‐induced local release events were comparable to the spontaneous Ca 2+ sparks, the elementary Ca 2+ events mediated via the ryanodine receptors. Our results, hence, show that the NAADP‐sensitive release channels are functionally expressed and Ca 2+ signals from the NAADP channel‐gated lysosomal stores cross‐activate ryanodine receptors to amplify Ca 2+ release in PASMCs.