CaR-mediated vasodilatation: Role of endothelium TRPC channels

Anthony Albert, Julia Shi, Jessica Mclough, Harry Z. E. Greenberg, Preet S. Chadha, Iain A. Greenwood, W. S. Vanessa Ho

Research output: Contribution to conferenceAbstractpeer-review

Abstract

There is increasing evidence that Ca2+-sensing G-protein-coupled receptors (CaR) have an important role in modulating vascular activity; both CaR-mediated contraction and dilation responses have been proposed. However, there is little information on mechanisms which govern CaR-mediated responses. The aim of the present work was to investigate endothelium-dependent actions of CaR stimulation on canonical transient receptor channels (TRPC) channel activity using patch clamp electrophysiology and functional studies. In cell-attached patches from freshly isolated endothelium cells of the rabbit mesenteric artery, bath application of CaCl2 (1–10 mM), and the CaR mimics calindol and AC265347 activated two distinct TRPC channels with TRPC1 and TRPC3/6/7 subtype properties. TRPC channel activities were inhibited by the negative modulator of CaR, calhex, and the phospholipase C inhibitor U73122. Wire myograph studies showed that CaR stimulation relaxed methoxyamine-contracted rabbit mesenteric arteries through an endothelium-dependent mechanism. Immunocytochemistry revealed CaR expression in both vascular smooth muscle and endothelium cells. The present work indicates that endothelium-dependent vasodilatations mediated by CaR are likely to involve activation of TRPC channels.
Original languageEnglish
Pages1056.1
DOIs
Publication statusPublished - Apr 2012

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