Evidence map›Paper›PMID 25142058›Full record

ArticleJournal of the American Heart Association2014

Activation of endothelial transient receptor potential C3 channel is required for small conductance calcium-activated potassium channel activation and sustained endothelial hyperpolarization and vasodilation of cerebral artery.

Mikhail Y Kochukov, Adithya Balasubramanian, Joel Abramowitz, Lutz Birnbaumer, Sean P Marrelli

Open access · goldAbstract read
In one paragraph

Article in Journal of the American Heart Association, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.4field-weighted citation impact, top 12% 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

35 citing papers in PubMed, 49 citations in OpenAlex.

  1. A pericyte chloride clamp mechanism governs capillary control of cerebral blood flow.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Review
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  7. Differential Effects of High Fat Diets on Resilience to HAntioxidants (Basel, Switzerland) · 2023
    Article
  8. Review
  9. KMicrocirculation (New York, N.Y. : 1994) · 2023
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  10. Review
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  12. Article
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  14. Review
  15. Aging Alters Cerebrovascular Endothelial GPCR and K+ Channel Function: Divergent Role of Biological Sex.The journals of gerontology. Series A, Biological sciences and medical sciences · 2020
    Article
  16. Endothelial CaThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2020
    Review
  17. The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes.Frontiers in cellular neuroscience · 2020
    Review
  18. Article
  19. Calcium signals that determine vascular resistance.Wiley interdisciplinary reviews. Systems biology and medicine · 2019
    Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Mikhail Y KochukovDepartment of Anesthesiology, Baylor College of Medicine, Houston, TX (M.Y.K., A.B., S.P.M.).
Adithya BalasubramanianDepartment of Anesthesiology, Baylor College of Medicine, Houston, TX (M.Y.K., A.B., S.P.M.).
Joel AbramowitzDivision of Intramural Research, National Institute of Environmental Health Sciences Research, Triangle Park, NC (J.A., L.B.).
Lutz BirnbaumerDivision of Intramural Research, National Institute of Environmental Health Sciences Research, Triangle Park, NC (J.A., L.B.).
Sean P MarrelliDepartment of Anesthesiology, Baylor College of Medicine, Houston, TX (M.Y.K., A.B., S.P.M.) Department of Physiology and Biophysics and Graduate Program in Physiology, Cardiovascular Sciences Track, Baylor College of Medicine, Houston, TX (S.P.M.).
Baylor College of Medicine · USNational Institute of Environmental Health Sciences · US

Funding

Transmembrane Signaling MechanismsZIAES101643 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI BIRNBAUMER, LUTZ · 2011 to 2014
$5.4M
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
Intramural NIH HHS Z01 ES101684NHLBI NIH HHS R01 HL088435NIEHS NIH HHS Z01-ES101684
6 · The paper itself

Abstract

backgroundTransient receptor potential C3 (TRPC3) has been demonstrated to be involved in the regulation of vascular tone through endothelial cell (EC) hyperpolarization and endothelium-dependent hyperpolarization-mediated vasodilation. However, the mechanism by which TRPC3 regulates these processes remains unresolved. We tested the hypothesis that endothelial receptor stimulation triggers rapid TRPC3 trafficking to the plasma membrane, where it provides the source of Ca(2+) influx for small conductance calcium-activated K(+) (SKCa) channel activation and sustained EC hyperpolarization. METHODS AND

resultsPressurized artery studies were performed with isolated mouse posterior cerebral artery. Treatment with a selective TRPC3 blocker (Pyr3) produced significant attenuation of endothelium-dependent hyperpolarization-mediated vasodilation and endothelial Ca(2+) response (EC-specific Ca(2+) biosensor) to intraluminal ATP. Pyr3 treatment also resulted in a reduced ATP-stimulated global Ca(2+) and Ca(2+) influx in primary cultures of cerebral endothelial cells. Patch-clamp studies with freshly isolated cerebral ECs demonstrated 2 components of EC hyperpolarization and K(+) current activation in response to ATP. The early phase was dependent on intermediate conductance calcium-activated K(+) channel activation, whereas the later sustained phase relied on SKC a channel activation. The SKC a channel-dependent phase was completely blocked with TRPC3 channel inhibition or in ECs of TRPC3 knockout mice and correlated with increased trafficking of TRPC3 (but not SKC a channel) to the plasma membrane.

conclusionsWe propose that TRPC3 dynamically regulates SKC a channel activation through receptor-dependent trafficking to the plasma membrane, where it provides the source of Ca(2+) influx for sustained SKC a channel activation, EC hyperpolarization, and endothelium-dependent hyperpolarization-mediated vasodilation.

Indexed as

AnimalsCalciumEndothelial CellsEndothelium, VascularMembrane PotentialsMiceMice, KnockoutPatch-Clamp TechniquesPosterior Cerebral ArterySmall-Conductance Calcium-Activated Potassium ChannelsTRPC Cation ChannelsVasodilationCalciumSmall-Conductance Calcium-Activated Potassium ChannelsTRPC3 cation channelTRPC Cation Channelscerebrovascular circulationendotheliumendothelium‐derived factorsion channelsvasculature

Identifiers

PMID25142058
PMCPMC4310376
OpenAlexW2163145087

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.