Capacitative Ca(2+) entry in agonist-induced pulmonary vasoconstriction.
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.
McDaniel
S S
SS
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California School of Medicine, San Diego, California 92103, USA.
Platoshyn
O
O
Wang
J
J
Yu
Y
Y
Sweeney
M
M
Krick
S
S
Rubin
L J
LJ
Yuan
J X
JX
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002469:Cell Separation; D004730:Endothelium, Vascular / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D066298:In Vitro Techniques; D007811:Lanthanum / Q000494:pharmacology; D008168:Lung / Q000098:blood supply*; D008297:Male; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D050052:TRPC Cation Channels; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D050052:TRPC Cation Channels; D014662:Vasoconstrictor Agents; C096351:transient receptor potential cation channel, subfamily C, member 1; D007811:Lanthanum; D009532:Nickel; D002118:Calcium