Transient receptor potential canonical type 3 channels facilitate endothelium-derived hyperpolarization-mediated resistance artery vasodilator activity

S Senadheera; Y Kim; T Hilton Grayson; S Toemoe; M Y Kochukov; J Abramowitz; G D Housley; R L Bertrand; P S Chadha; P P Bertrand; T V Murphy; M Tare; L Birnbaumer; S P Marrelli; Shaun L Sandow

doi:10.1093/cvr/cvs208

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Transient receptor potential canonical type 3 channels facilitate endothelium-derived hyperpolarization-mediated resistance artery vasodilator activity

Journal article

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Transient receptor potential canonical type 3 channels facilitate endothelium-derived hyperpolarization-mediated resistance artery vasodilator activity

S Senadheera, Y Kim, T Hilton Grayson, S Toemoe, M Y Kochukov, J Abramowitz, G D Housley, R L Bertrand, P S Chadha, P P Bertrand, …

Cardiovascular Research, Vol.95(4), pp.439-447

2012

DOI: https://doi.org/10.1093/cvr/cvs208

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Abstract

endothelium

calcium channel

potassium channel

signalling microdomain

smooth muscle

vasodilation

Aims Microdomain signalling mechanisms underlie key aspects of artery function and the modulation of intracellular calcium, with transient receptor potential (TRP) channels playing an integral role. This study determines the distribution and role of TRP canonical type 3 (C3) channels in the control of endothelium-derived hyperpolarization (EDH)-mediated vasodilator tone in rat mesenteric artery. Methods and resultsTRPC3 antibody specificity was verified using rat tissue, human embryonic kidney (HEK)-293 cells stably transfected with mouse TRPC3 cDNA, and TRPC3 knock-out (KO) mouse tissue using western blotting and confocal and ultrastructural immunohistochemistry. TRPC3-Pyr3 (ethyl-1-(4-(2,3,3-trichloroacrylamide)phenyl)-5-(trifluoromethyl) -1H-pyrazole-4-carboxylate) specificity was verified using patch clamp of mouse mesenteric artery endothelial and TRPC3-transfected HEK cells, and TRPC3 KO and wild-type mouse aortic endothelial cell calcium imaging and mesenteric artery pressure myography. TRPC3 distribution, expression, and role in EDH-mediated function were examined in rat mesenteric artery using immunohistochemistry and western blotting, and pressure myography and endothelial cell membrane potential recordings. In rat mesenteric artery, TRPC3 was diffusely distributed in the endothelium, with approximately five-fold higher expression at potential myoendothelial microdomain contact sites, and immunoelectron microscopy confirmed TRPC3 at these sites. Western blotting and endothelial damage confirmed primary endothelial TRPC3 expression. In rat mesenteric artery endothelial cells, Pyr3 inhibited hyperpolarization generation, and with individual SKCa (apamin) or IKCa (TRAM-34) block, Pyr3 abolished the residual respective IKCa- and SKCa-dependent EDH-mediated vasodilation. ConclusionThe spatial localization of TRPC3 and associated channels, receptors, and calcium stores are integral for myoendothelial microdomain function. TRPC3 facilitates endothelial SKCa and IKCa activation, as key components of EDH-mediated vasodilator activity and for regulating mesenteric artery tone. © 2012 The Author.

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Title: Transient receptor potential canonical type 3 channels facilitate endothelium-derived hyperpolarization-mediated resistance artery vasodilator activity
Authors: S Senadheera (Author) - University of New South Wales
Y Kim (Author) - University of New South Wales
T Hilton Grayson (Author) - University of New South Wales
S Toemoe (Author) - University of New South Wales
M Y Kochukov (Author) - Baylor College of Medicine, United States
J Abramowitz (Author) - National Institute of Environmental Health Sciences, United States
G D Housley (Author) - University of New South Wales
R L Bertrand (Author) - University of New South Wales
P S Chadha (Author) - University of New South Wales
P P Bertrand (Author) - University of New South Wales
T V Murphy (Author) - University of New South Wales
M Tare (Author) - Monash University
L Birnbaumer (Author) - National Institute of Environmental Health Sciences, United States
S P Marrelli (Author) - Baylor College of Medicine, United States
Shaun L Sandow (Author) - University of New South Wales
Publication details: Cardiovascular Research, Vol.95(4), pp.439-447
Publisher: Oxford University Press
Date published: 2012
DOI: 10.1093/cvr/cvs208
ISSN: 0008-6363
Copyright note: Copyright © 2012 The Author. This is a pre-copyedited, author-produced PDF of an article accepted for publication in Cardiovascular Research following peer review. The definitive publisher-authenticated version is available online at http://dx.doi.org/10.1093/cvr/cvs208. Published on behalf of the European Society of Cardiology. All rights reserved. For permissions please email: journals.permissions@oup.com.
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: 99448962202621
Output Type: Journal article

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Web Of Science research areas: Cardiac & Cardiovascular Systems

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