TRPC3 channels facilitate KCa-mediated endothelial vasodilator activity in rat mesenteric artery

S Senadheera; Y Kim; S Toemoe; P P Bertrand; M Y Kochukov; T V Murphy; S P Marrelli; M Tare; Shaun L Sandow

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TRPC3 channels facilitate KCa-mediated endothelial vasodilator activity in rat mesenteric artery

Abstract

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TRPC3 channels facilitate KCa-mediated endothelial vasodilator activity in rat mesenteric artery

S Senadheera, Y Kim, S Toemoe, P P Bertrand, M Y Kochukov, T V Murphy, S P Marrelli, M Tare and Shaun L Sandow

FASEB Journal, Vol.25(1082.5)

2011

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Abstract

Biochemistry and Cell Biology

Physiology

Medical Physiology

endothelial vasodilator activity

rat mesenteric artery

The distribution and role of TRPC3 channel microdomain signalling sites in rat mesenteric artery were examined using rat and TRPC3 KO mouse tissue and TRPC3-transfected HEK cells. Expression was studied by confocal and ultrastructural immunohistochemistry and function was measured by pressure myography and membrane potential recording. Endothelial TRPC3 expression was verified by Western blotting; localization to endothelial cells was determined by comparing endothelium intact and denuded arteries. Confocal immunohistochemistry demonstrated diffuse TRPC3 in mesenteric artery endothelium, with fluorescence density being ~5 fold higher at myoendothelial microdomain sites, with immunoelectron microscopy confirming TRPC3 at these latter sites. TRPC3 was absent in smooth muscle of rat mesenteric artery, but present in mouse aortic smooth muscle and endothelium. The putative TRPC3 inhibitor Pyr3 blocked current changes in patch clamped TRPC3 transfected HEK cells and inhibited KCa-mediated endothelium-derived hyperpolarization activity in rat mesenteric artery. The Pyr3 block appears to be specific to TRPC3 since it inhibited carbachol-induced calcium flux in aortic endothelial cells isolated from TRPC3 WT, but not KO mice. In summary, TRPC3 function and localization in rat mesenteric artery is consistent with a critical role in control of tone in this vessel. Supported by NHMRC and NIH.

Details

Title: TRPC3 channels facilitate KCa-mediated endothelial vasodilator activity in rat mesenteric artery
Authors: S Senadheera (Author) - University of New South Wales
Y Kim (Author) - University of New South Wales
S Toemoe (Author) - University of New South Wales
P P Bertrand (Author) - University of New South Wales
M Y Kochukov (Author) - Baylor College of Medicine, United States
T V Murphy (Author) - University of New South Wales
S P Marrelli (Author) - University of New South Wales
M Tare (Author) - Monash University
Shaun L Sandow (Author) - University of New South Wales
Publication details: FASEB Journal, Vol.25(1082.5)
Publisher: Federation of American Societies for Experimental Biology
Date published: 2011
ISSN: 0892-6638
Organisation Unit: School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99448641702621
Output Type: Abstract

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