Evidence map›Paper›PMID 26503181›Full record

ArticleThe Journal of physiology2015

Fundamental role for the KCNE4 ancillary subunit in Kv7.4 regulation of arterial tone.

Thomas A Jepps, Georgina Carr, Pia R Lundegaard, Søren-Peter Olesen, Iain A Greenwood

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

48 citing papers in PubMed, 66 citations in OpenAlex.

  1. Identification of Sodium/Myo-Inositol Transporter 1 as a Major Determinant of Arterial Contractility.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  2. Uncovering a Sex-Specific cAMP Landscape in Vascular Smooth Muscle.bioRxiv : the preprint server for biology · 2026
    Article
  3. KCommunications medicine · 2026
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  13. KCNQ Potassium Channels as Targets of Botanical Folk Medicines.Annual review of pharmacology and toxicology · 2022
    Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. The agonistic action of URO-K10 on Kv7.4 and 7.5 channels is attenuated by co-expression of KCNE4 ancillary subunit.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2020
    Article
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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 3 institutions in 2 countries.

Thomas A JeppsIon Channels Group, Department of Biomedical Sciences, University of Copenhagen, Denmark.
Georgina CarrVascular Biology Research Centre, Institute for Cardiovascular and Cell Sciences, St George's University of London, London, UK.
Pia R LundegaardIon Channels Group, Department of Biomedical Sciences, University of Copenhagen, Denmark.
Søren-Peter OlesenIon Channels Group, Department of Biomedical Sciences, University of Copenhagen, Denmark.
Iain A GreenwoodIon Channels Group, Department of Biomedical Sciences, University of Copenhagen, Denmark.
IT University of Copenhagen · DKUniversity of Copenhagen · DKSt George's, University of London · GB

Funding

Medical Research Council MR/K019074/1
6 · The paper itself

Abstract

key pointsKCNE4 alters the biophysical properties and cellular localization of voltage-gated potassium channel Kv7.4. KCNE4 is expressed in a variety of arteries and, in mesenteric arteries, co-localizes with Kv7.4, which is important in the control of vascular contractility. Knockdown of KCNE4 leads to reduced Kv7.4 membrane abundance, a depolarized membrane potential and an augmented response to vasoconstrictors. KCNE4 is a key regulator of the function and expression of Kv7.4 in vascular smooth muscle. ABSTRACT: The KCNE ancillary subunits (KCNE1-5) significantly alter the expression and function of voltage-gated potassium channels; however, their role in the vasculature has yet to be determined. The present study aimed to investigate the expression and function of the KCNE4 subunit in rat mesenteric arteries and to determine whether it has a functional impact on the regulation of arterial tone by Kv7 channels. In HEK cells expressing Kv7.4, co-expression of KCNE4 increased the membrane expression of Kv7.4 and significantly altered Kv7.4 current properties. Quantitative PCR analysis of different rat arteries found that the KCNE4 isoform predominated and proximity ligation experiments showed that KCNE4 co-localized with Kv7.4 in mesenteric artery myocytes. Morpholino-induced knockdown of KCNE4 depolarized mesenteric artery smooth muscle cells and resulted in their increased sensitivity to methoxamine being attenuated (mean ± SEM EC50 decreased from 5.7 ± 0.63 μm to 1.6 ± 0.23 μm), which coincided with impaired effects of Kv7 modulators. When KCNE4 expression was reduced, less Kv7.4 expression was found in the membrane of the mesenteric artery myocytes. These data show that KCNE4 is consistently expressed in a variety of arteries, and knockdown of the expression product leads to reduced Kv7.4 membrane abundance, a depolarized membrane potential and an augmented response to vasoconstrictors. The present study is the first to demonstrate an integral role of KCNE4 in regulating the function and expression of Kv7.4 in vascular smooth muscle.

Indexed as

VasoconstrictionAnimalsCells, CulturedHEK293 CellsHumansMaleMembrane PotentialsMesenteric ArteriesMuscle, Smooth, VascularPotassium Channels, Voltage-GatedRatsRats, WistarKCNE4 protein, ratPotassium Channels, Voltage-Gated

Identifiers

PMID26503181
PMCPMC4704525
OpenAlexW1836533390

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.