Evidence map›Paper›PMID 24778429›Full record

ArticleThe Journal of general physiology2014

Local control of TRPV4 channels by AKAP150-targeted PKC in arterial smooth muscle.

Jose Mercado, Rachael Baylie, Manuel F Navedo, Can Yuan, John D Scott, Mark T Nelson, Joseph E Brayden, Luis F Santana

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of general physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
5.5field-weighted citation impact, top 3% 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

75 citing papers in PubMed, 108 citations in OpenAlex.

  1. Review
  2. Review
  3. Pacemaking in the lymphatic system.The Journal of physiology · 2026
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  13. Review
  14. Electro-metabolic signaling.The Journal of general physiology · 2024
    Article
  15. Article
  16. Vascular mechanotransduction.Physiological reviews · 2023
    Review
  17. Novel Smooth Muscle CaCirculation · 2022
    Article
  18. Review
  19. Article
  20. Glucosylsphingosine evokes pruritus via activation of 5-HTBritish journal of pharmacology · 2022
    Article

15 more citing papers are in PubMed but not listed here.

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

8 authors at 4 institutions in 1 country.

Jose MercadoDepartment of Physiology & Biophysics and 2 Howard Hughes Medical Institute, Department of Pharmacology, University of Washington, Seattle, WA 98195.
Rachael Baylie
Manuel F Navedo
Can Yuan
John D Scott
Mark T Nelson
Joseph E Brayden
Luis F Santana
University of Vermont · USUniversity of Washington · USHoward Hughes Medical Institute · USUniversity of California, Davis · US

Funding

Proteomics Core for Neuroscience P20 RR16435P20RR016435 · NCRR · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI SPEES, JEFFREY L · 2001 to 2010
$23.5M
Impact of SAH on Parenchymal Arterioles and Neurovascular CouplingP01HL095488 · NHLBI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI BONEV, ADRIAN · 2010 to 2014
$11.4M
NEUROSCIENCE TRAINING PROGRAMT32GM007507 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI HALLORAN, MARY C · 1985 to 2017
$9.3M
Center for Neuroscience ExcellenceP30GM103498 · NIGMS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI PARSONS, RODNEY L · 2012 to 2015
$4.3M
REGULATION OF CEREBRAL ARTERY DILATIONR01HL044455 · NHLBI · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI NELSON, MARK T · 1991 to 2010
$3.9M
Persistent Calcium Sparklets in Vascular Smooth MuscleR01HL085870 · NHLBI · UNIVERSITY OF WASHINGTON · PI SANTANA, LUIS F · 2007 to 2016
$3.9M
Calcium Sparklets-Induced Vascular Dysfunction During DiabetesR01HL098200 · NHLBI · UNIVERSITY OF WASHINGTON · PI NAVEDO, MANUEL F · 2010 to 2019
$3.5M
Ca2+ Sparks and Urinary Bladder Smooth Muscle ExcitabilityR37DK053832 · NIDDK · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI NELSON, MARK T · 2008 to 2017
$3.4M
Molecular Analysis of Anchoring ProteinsR37GM048231 · NIGMS · UNIVERSITY OF WASHINGTON · PI SCOTT, JOHN D · 2004 to 2013
$2.7M
CA++ SPARKS &URINARY BLADDER SMOOTH MUSCLE EXCITABILITYR01DK053832 · NIDDK · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI NELSON, MARK T · 1998 to 2006
$2.0M
MOLECULAR ANALYSIS OF PKA-ANCHORING PROTEIN INTERACTIONR01GM048231 · NIGMS · OREGON HEALTH AND SCIENCE UNIVERSITY · PI SCOTT, JOHN D · 1992 to 2003
$858k
Endothelial KCa channels, Ca2+ signaling & arteriolar function in the brainR01HL098243 · NHLBI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI NELSON, MARK T · 2010 to 2010
$269k
NCRR NIH HHS 2-P20-RR-016435-06NCRR NIH HHS P20 RR016435NHLBI NIH HHS HL085870NHLBI NIH HHS HL098200NHLBI NIH HHS HL098243NHLBI NIH HHS HL44455NHLBI NIH HHS P01 HL095488NHLBI NIH HHS P01HL095488NHLBI NIH HHS R01 HL044455NHLBI NIH HHS R01 HL085870NHLBI NIH HHS R01 HL098200NHLBI NIH HHS R01 HL098243NIDDK NIH HHS R01 DK053832NIDDK NIH HHS R37 DK053832NIDDK NIH HHS R37DK053832NIGMS NIH HHS GM048231NIGMS NIH HHS P30 GM103498NIGMS NIH HHS R01 GM048231NIGMS NIH HHS R37 GM048231NIGMS NIH HHS T32 GM007507
6 · The paper itself

Abstract

Transient receptor potential vanilloid 4 (TRPV4) channels are Ca(2+)-permeable, nonselective cation channels expressed in multiple tissues, including smooth muscle. Although TRPV4 channels play a key role in regulating vascular tone, the mechanisms controlling Ca(2+) influx through these channels in arterial myocytes are poorly understood. Here, we tested the hypothesis that in arterial myocytes the anchoring protein AKAP150 and protein kinase C (PKC) play a critical role in the regulation of TRPV4 channels during angiotensin II (AngII) signaling. Super-resolution imaging revealed that TRPV4 channels are gathered into puncta of variable sizes along the sarcolemma of arterial myocytes. Recordings of Ca(2+) entry via single TRPV4 channels ("TRPV4 sparklets") suggested that basal TRPV4 sparklet activity was low. However, Ca(2+) entry during elementary TRPV4 sparklets was ∼ 100-fold greater than that during L-type CaV1.2 channel sparklets. Application of the TRPV4 channel agonist GSK1016790A or the vasoconstrictor AngII increased the activity of TRPV4 sparklets in specific regions of the cells. PKC and AKAP150 were required for AngII-induced increases in TRPV4 sparklet activity. AKAP150 and TRPV4 channel interactions were dynamic; activation of AngII signaling increased the proximity of AKAP150 and TRPV4 puncta in arterial myocytes. Furthermore, local stimulation of diacylglycerol and PKC signaling by laser activation of a light-sensitive Gq-coupled receptor (opto-α1AR) resulted in TRPV4-mediated Ca(2+) influx. We propose that AKAP150, PKC, and TRPV4 channels form dynamic subcellular signaling domains that control Ca(2+) influx into arterial myocytes.

Indexed as

Calcium SignalingA Kinase Anchor ProteinsAngiotensin IIAnimalsArteriesCell LineHumansLeucineMiceMice, Inbred C57BLMuscle, Smooth, VascularProtein BindingProtein Kinase CRatsRats, Sprague-DawleySulfonamidesAkap5 protein, ratA Kinase Anchor ProteinsAngiotensin IILeucineN-(1-((4-(2-(((2,4-dichlorophenyl)sulfonyl)amino)-3-hydroxypropanoyl)-1-piperazinyl)carbonyl)-3-methylbutyl)-1-benzothiophene-2-carboxamideProtein Kinase CSulfonamidesTRPV Cation Channels

Identifiers

PMID24778429
PMCPMC4003184
OpenAlexW1987584620

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.