Store-operated channels mediate Ca(2+) influx and contraction in rat pulmonary artery

Cation channels activated by Ca(2+) store depletion have been proposed to mediate Ca(2+) influx in vascular smooth muscle cells. The aim of this study was to determine if store-operated channels have a functional role in pulmonary artery smooth muscle cells (PASMCs). In intact rat pulmonary artery r...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Circulation research 2001-11, Vol.89 (10), p.923-929
Hauptverfasser: Ng, L C, Gurney, A M
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Cation channels activated by Ca(2+) store depletion have been proposed to mediate Ca(2+) influx in vascular smooth muscle cells. The aim of this study was to determine if store-operated channels have a functional role in pulmonary artery smooth muscle cells (PASMCs). In intact rat pulmonary artery rings, cyclopiazonic acid (CPA) produced a sustained contraction that was resistant to inhibition by nifedipine, but abolished in Ca(2+)-free solution and 50% blocked in the presence of 6 micromol/L Cd(2+), 10 micromol/L Ni(2+), 600 micromol/L La(3+), and 7 micromol/L SKF96365. In freshly isolated PASMCs loaded with fura-2, CPA increased the intracellular Ca(2+) concentration by stimulating dihydropyridine-resistant Ca(2+) influx, which was approximately 50% blocked by 10 micromol/L Ni(2+) and 7 micromol/L SKF96365. In perforated-patch recordings, CPA activated a sustained inward current at negative membrane potentials, which persisted in cells dialyzed with BAPTA, showed a near linear dependence on membrane potential when Cs(+) was the main intracellular cation, and was blocked by Ni(2+), Cd(2+), and SKF96365 at concentrations preventing contraction. The current showed a bimodal dependence on extracellular Ca(2+), being enhanced 2-fold in the absence of Ca(2+) and around 10-fold on reducing Ca from 1.8 to 0.2 mmol/L. RT-PCR revealed the expression of Trp1, Trp3, Trp4, Trp5, and Trp6 mRNA, whereas immunostaining identified Trp1, Trp3, Trp4, and Trp6 channel proteins in isolated PASMCs. At least one of these subunits may contribute to cation channels in PASMCs, which are activated by store depletion to bring about Ca(2+) influx and contraction.
ISSN:0009-7330
1524-4571
DOI:10.1161/hh2201.100315