Capacitative Ca(2+) entry in agonist-induced pulmonary vasoconstriction

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 280; no. 5; pp. L870 - L880
• Main Authors: McDaniel, S S, Platoshyn, O, Wang, J, Yu, Y, Sweeney, M, Krick, S, Rubin, L J, Yuan, J X
• Format: Journal Article
• Language: English
• Published: United States 01.05.2001
• Subjects: Animals; Calcium - metabolism; Calcium - pharmacology; Calcium Channel Blockers - pharmacology; Calcium Channels - metabolism; Cell Separation; Endothelium, Vascular - metabolism; Extracellular Space - metabolism; In Vitro Techniques; Lanthanum - pharmacology; Lung - blood supply; Male; Nickel - pharmacology; Patch-Clamp Techniques; Pulmonary Artery - drug effects; Pulmonary Artery - metabolism; Rats; TRPC Cation Channels; Vasoconstriction - drug effects; Vasoconstriction - physiology; Vasoconstrictor Agents - pharmacology
• ISSN: 1040-0605
• DOI: 10.1152/ajplung.2001.280.5.l870

Agonist-induced increases in cytosolic Ca(2+) concentration ([Ca(2+)](cyt)) in pulmonary artery (PA) smooth muscle cells (SMCs) consist of a transient Ca(2+) release from intracellular stores followed by a sustained Ca(2+) influx. Depletion of intracellular Ca(2+) stores triggers capacitative Ca(2+) entry (CCE), which contributes to the sustained increase in [Ca(2+)](cyt) and the refilling of Ca(2+) into the stores. In isolated PAs superfused with Ca(2+)-free solution, phenylephrine induced a transient contraction, apparently by a rise in [Ca(2+)](cyt) due to Ca(2+) release from the intracellular stores. The transient contraction lasted for 3-4 min until the Ca(2+) store was depleted. Restoration of extracellular Ca(2+) in the presence of phentolamine produced a contraction potentially due to a rise in [Ca(2+)](cyt) via CCE. The store-operated Ca(2+) channel blocker Ni(2+) reduced the store depletion-activated Ca(2+) currents, decreased CCE, and inhibited the CCE-mediated contraction. In single PASMCs, we identified, using RT-PCR, five transient receptor potential gene transcripts. These results suggest that CCE, potentially through transient receptor potential-encoded Ca(2+) channels, plays an important role in agonist-mediated PA contraction.