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This Article Full Text Full Text (PDF) All Versions of this Article: 295/6/H2466    most recent 00639.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Boittin, F.-X. Articles by Bény, J.-L. Search for Related Content PubMed PubMed Citation Articles by Boittin, F.-X. Articles by Bény, J.-L.

Ca²⁺-independent PLA₂ controls endothelial store-operated Ca²⁺ entry and vascular tone in intact aorta

Department of Zoology and Animal Biology, Laboratory of Vascular Cell Physiology, University of Geneva, Geneva, Switzerland

Submitted 15 July 2008 ; accepted in final form 13 October 2008

During an agonist stimulation of endothelial cells, the sustained Ca²⁺ entry occurring through store-operated channels has been shown to significantly contribute to smooth muscle relaxation through the release of relaxing factors such as nitric oxide (NO). However, the mechanisms linking Ca²⁺ stores depletion to the opening of such channels are still elusive. We have used Ca²⁺ and tension measurements in intact aortic strips to investigate the role of the Ca²⁺-independent isoform of phospholipase A₂ (iPLA₂) in endothelial store-operated Ca²⁺ entry and endothelium-dependent relaxation of smooth muscle. We provide evidence that iPLA₂ is involved in the activation of endothelial store-operated Ca²⁺ entry when Ca²⁺ stores are artificially depleted. We also show that the sustained store-operated Ca²⁺ entry occurring during physiological stimulation of endothelial cells with the circulating hormone ATP is due to iPLA₂ activation and significantly contributes to the amplitude and duration of ATP-induced endothelium-dependent relaxation. Consistently, both iPLA₂ metabolites arachidonic acid and lysophosphatidylcholine were found to stimulate Ca²⁺ entry in native endothelial cells. However, only the latter triggered endothelium-dependent relaxation through NO release, suggesting that lysophosphatidylcholine produced by iPLA₂ upon Ca²⁺ stores depletion may act as an intracellular messenger that stimulates store-operated Ca²⁺ entry and subsequent NO production in endothelial cells. Finally, we found that ACh-induced endothelium relaxation also depends on iPLA₂ activation, suggesting that the iPLA₂-dependent control of endothelial store-operated Ca²⁺ entry is a key physiological mechanism regulating arterial tone.

endothelial cells; calcium imaging; calcium-independent isoform of phospholipase A₂; store-operated channels; endothelium-dependent relaxation

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