Evidence map›Paper›PMID 22180649›Full record

ArticleAmerican journal of physiology. Heart and circulatory physiology2012

KCNE2 protein is more abundant in ventricles than in atria and can accelerate hERG protein degradation in a phosphorylation-dependent manner.

Mei Zhang, Yuhong Wang, Min Jiang, Dimitar P Zankov, Sabeeha Chowdhury, Vigneshwar Kasirajan, Gea-Ny Tseng

Abstract read
In one paragraph

Article in American journal of physiology. Heart and circulatory physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.1field-weighted citation impact, top 11% 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

16 citing papers in PubMed, 25 citations in OpenAlex.

  1. KCommunications medicine · 2026
    Article
  2. Review
  3. The ERG1 KFrontiers in molecular neuroscience · 2022
    Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Single nucleotide polymorphisms in proximity to K-channel genes are associated with decreased longitudinal QTc variance.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2014
    Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. 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

7 authors at 1 institution in 1 country.

Mei ZhangDepartment of Physiology and Biophysics, Medical College of Virginia at Virginia Commonwealth University, Richmond, VA 23298, USA.
Yuhong Wang
Min Jiang
Dimitar P Zankov
Sabeeha Chowdhury
Vigneshwar Kasirajan
Gea-Ny Tseng
Virginia Commonwealth University Medical Center · US

Funding

VCU Neuroscience Center Core GrantP30NS047463 · NINDS · VIRGINIA COMMONWEALTH UNIVERSITY · PI POVLISHOCK, JOHN T · 2003 to 2013
$5.0M
POST INFARCTION K CHANNEL REMODELING/MOLECULAR MECHANISMR01HL067840 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI TSENG, GEA-NY · 2001 to 2010
$2.2M
STRUCTURE-FUNCTION RELATION & MODULATION OF Kv CHANNELSR01HL107294 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI TSENG, GEA-NY · 2012 to 2015
$1.5M
NHLBI NIH HHS R01 HL107294NHLBI NIH HHS R01 HL-67840NINDS NIH HHS P30 NS047463
6 · The paper itself

Abstract

KCNE2 functions as an auxiliary subunit in voltage-gated K and HCN channels in the heart. Genetic variations in KCNE2 have been linked to long QT syndrome. The underlying mechanisms are not entirely clear. One of the issues is whether KCNE2 protein is expressed in ventricles. We use adenovirus-mediated genetic manipulations of adult cardiac myocytes to validate two antibodies (termed Ab1 and Ab2) for their ability to detect native KCNE2 in the heart. Ab1 faithfully detects native KCNE2 proteins in spontaneously hypertensive rat and guinea pig hearts. In both cases, KCNE2 protein is more abundant in ventricles than in atria. In both ventricular and atrial myocytes, KCNE2 protein is preferentially distributed on the cell surface. Ab1 can detect a prominent KCNE2 band in human ventricular muscle from nonfailing hearts. The band intensity is much fainter in atria and in failing ventricles. Ab2 specifically detects S98 phosphorylated KCNE2. Through exploring the functional significance of S98 phosphorylation, we uncover a novel mechanism by which KCNE2 modulates the human ether-a-go-go related gene (hERG) current amplitude: by accelerating hERG protein degradation and thus reducing the hERG protein level on the cell surface. S98 phosphorylation appears to be required for this modulation, so that S98 dephosphorylation leads to an increase in hERG/rapid delayed rectifier current amplitude. Our data confirm that KCNE2 protein is expressed in the ventricles of human and animal models. Furthermore, KCNE2 can modulate its partner channel function not only by altering channel conductance and/or gating kinetics, but also by affecting protein stability.

Indexed as

ProteolysisAmino Acid SequenceAnimalsCells, CulturedDogsFemaleGuinea PigsHeart AtriaHeart VentriclesHumansMaleModels, AnimalMolecular Sequence DataMyocytes, CardiacPatch-Clamp TechniquesPhosphorylationERG protein, humanKCNE2 protein, humanKCNE2 protein, ratPotassium Channels, Voltage-GatedShal Potassium ChannelsTrans-ActivatorsTranscriptional Regulator ERG

Identifiers

PMID22180649
PMCPMC3322735
OpenAlexW2156563853

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.