Nicotinic acid adenine dinucleotide phosphate mediates Ca2+ signals and contraction in arterial smooth muscle via a two-pool mechanism

F-X Boittin, A Galione, Anthony Mark Evans

Research output: Contribution to journalArticlepeer-review

103 Citations (Scopus)

Abstract

Previous studies of arterial smooth muscle have shown that inositol 1,4,5-trisphosphate (IP3) and cyclic ADP-ribose mobilize Ca2+ from the sarcoplasmic reticulum. In contrast, little is known about Ca2+ mobilization by nicotinic acid adenine dinucleotide phosphate, a pyridine nucleotide derived from beta-NADP(+). We show here that intracellular dialysis of nicotinic acid adenine dinucleotide phosphate (NAADP) induces spatially restricted "bursts" of Ca2+ release that initiate a global Ca2+ wave and contraction in pulmonary artery smooth muscle cells. Depletion of sarcoplasmic reticulum Ca2+ stores with thapsigargin and inhibition of ryanodine receptors with ryanodine, respectively, block the global Ca2+ waves by NAADP. Under these conditions, however, localized Ca2+ bursts are still observed. In contrast, xestospongin C, an IP3 receptor antagonist, had no effect on Ca2+ signals by NAADP. We propose that NAADP mobilizes Ca2+ via a 2-pool mechanism, and that initial Ca2+ bursts are amplified by subsequent sarcoplasmic reticulum Ca2+ release via ryanodine receptors but not via IP3 receptors.

Original languageEnglish
Pages (from-to)1168-1175
Number of pages8
JournalCirculation Research
Volume91
Issue number12
DOIs
Publication statusPublished - 13 Dec 2002

Keywords

  • NAADP
  • calcium
  • smooth muscle
  • sarcoplasmic reticulum
  • ryanodine receptors
  • CYCLIC ADP-RIBOSE
  • SEA-URCHIN EGGS
  • INOSITOL TRISPHOSPHATE
  • GENE-EXPRESSION
  • CALCIUM SPARKS
  • RELEASE
  • RECEPTOR
  • MYOCYTES
  • STORES

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