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 language | English |
---|---|
Pages (from-to) | 1168-1175 |
Number of pages | 8 |
Journal | Circulation Research |
Volume | 91 |
Issue number | 12 |
DOIs | |
Publication status | Published - 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