Evidence map›Paper›PMID 22721989›Full record

ArticleCardiovascular research2012

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

Sevvandi Senadheera, Youngsoo Kim, T Hilton Grayson, Sianne Toemoe, Mikhail Y Kochukov, Joel Abramowitz, Gary D Housley, Rebecca L Bertrand, Preet S Chadha, Paul P Bertrand and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Cardiovascular research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
9.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 85 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Article
  5. Review
  6. Role of TRP Channels in Metabolism-Related Diseases.International journal of molecular sciences · 2024
    Review
  7. Cracking the Endothelial Calcium (CaInternational journal of molecular sciences · 2023
    Review
  8. Review
  9. Article
  10. Endothelial CaThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2020
    Review
  11. Article
  12. KFrontiers in physiology · 2020
    Article
  13. Calcium signals that determine vascular resistance.Wiley interdisciplinary reviews. Systems biology and medicine · 2019
    Review
  14. Review
  15. Article
  16. Article
  17. Functional Interaction among KInternational journal of molecular sciences · 2019
    Review
  18. Review
  19. Article
  20. The Role of Endothelial CaInternational journal of molecular sciences · 2018
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 3 countries.

Sevvandi SenadheeraDepartment of Physiology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney 2052, Australia. s.senadheera@student.unsw.edu.au
Youngsoo Kim
T Hilton Grayson
Sianne Toemoe
Mikhail Y Kochukov
Joel Abramowitz
Gary D Housley
Rebecca L Bertrand
Preet S Chadha
Paul P Bertrand
Timothy V Murphy
Marianne Tare
Lutz Birnbaumer
Sean P Marrelli
Shaun L Sandow
University of Sydney · AUUNSW Sydney · AUBaylor College of Medicine · USNational Institute of Environmental Health Sciences · USMonash University · AU

Funding

Transmembrane Signaling Mechanisms Involving TRP ChannelsZIAES101684 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI BIRNBAUMER, LUTZ · 2011 to 2014
$3.2M
Transmembrane Signaling Mechanisms Involving TRP ChannelsZ01ES101684 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI BIRNBAUMER, LUTZ · 2003 to 2008
$2.1M
Mechanisms of Endothelial Cell HyperpolarizationR01HL088435 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI MARRELLI, SEAN P · 2008 to 2012
$1.9M
NHLBI NIH HHS R01 HL088435NIEHS NIH HHS Z01-ES-101684
6 · The paper itself

Abstract

aimsMicrodomain 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 SK(Ca) (apamin) or IK(Ca) (TRAM-34) block, Pyr3 abolished the residual respective IK(Ca)- and SK(Ca)-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 SK(Ca) and IK(Ca) activation, as key components of EDH-mediated vasodilator activity and for regulating mesenteric artery tone.

Indexed as

VasodilationAnimalsArterial PressureBiological FactorsBlotting, WesternCalciumDose-Response Relationship, DrugEndothelium, VascularHEK293 CellsHumansImmunohistochemistryIntermediate-Conductance Calcium-Activated Potassium ChannelsMaleMembrane PotentialsMesenteric ArteriesMiceBiological FactorsCalciumendothelium-dependent hyperpolarization factorIntermediate-Conductance Calcium-Activated Potassium ChannelsPotassium Channel BlockersSmall-Conductance Calcium-Activated Potassium ChannelsTRPC3 cation channelTRPC Cation ChannelsVasodilator Agents

Identifiers

PMID22721989
PMCPMC3422079
OpenAlexW2168924147

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.