Evidence map›Paper›PMID 27005320›Full record

ArticleScientific reports2016

Human EAG channels are directly modulated by PIP2 as revealed by electrophysiological and optical interference investigations.

Bo Han, Kunyan He, Chunlin Cai, Yin Tang, Linli Yang, Stefan H Heinemann, Toshinori Hoshi, Shangwei Hou

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

14 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Modulation of Lymphocyte Potassium Channel KACS pharmacology & translational science · 2020
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Potassium Channel Gain of Function in Epilepsy: An Unresolved Paradox.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2018
    Article
  10. Article
  11. Ether-à-go-go KThe Journal of physiology · 2018
    Review
  12. Article
  13. Eag1 KOxidative medicine and cellular longevity · 2017
    Review
  14. Article
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 3 countries.

Bo HanKey Laboratory of Systems Biomedicine (Ministry of Education), Institute of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
Kunyan HeKey Laboratory of Systems Biomedicine (Ministry of Education), Institute of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
Chunlin CaiKey Laboratory of Systems Biomedicine (Ministry of Education), Institute of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
Yin TangKey Laboratory of Systems Biomedicine (Ministry of Education), Institute of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
Linli YangKey Laboratory of Systems Biomedicine (Ministry of Education), Institute of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
Stefan H HeinemannCenter for Molecular Biomedicine, Department of Biophysics, Friedrich Schiller University Jena &Jena University Hospital, Hans-Knöll-Str. 2, D-07745 Jena, Germany.
Toshinori HoshiDepartment of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Shangwei HouKey Laboratory of Systems Biomedicine (Ministry of Education), Institute of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
Shanghai Jiao Tong University · CNJena University Hospital · DEShanghai Cancer Institute · CNUniversity of Pennsylvania · US

Funding

REGULATION OF ION CHANNELS BY METHIONINE OXIDATIONR01GM057654 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI HOSHI, TOSHINORI, OLCESE, RICCARDO · 1998 to 2014
$5.0M
NIGMS NIH HHS R01 GM057654NIGMS NIH HHS R01GM057654
6 · The paper itself

Abstract

Voltage-gated ether à go-go (EAG) K(+) channels are expressed in various types of cancer cells and also in the central nervous system. Aberrant overactivation of human EAG1 (hEAG1) channels is associated with cancer and neuronal disorders such as Zimmermann-Laband and Temple-Baraitser syndromes. Although hEAG1 channels are recognized as potential therapeutic targets, regulation of their functional properties is only poorly understood. Here, we show that the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) is a potent inhibitory gating modifier of hEAG1 channels. PIP2 inhibits the channel activity by directly binding to a short N-terminal segment of the channel important for Ca(2+)/calmodulin (CaM) binding as evidenced by bio-layer interferometry measurements. Conversely, depletion of endogenous PIP2 either by serotonin-induced phospholipase C (PLC) activation or by a rapamycin-induced translocation system enhances the channel activity at physiological membrane potentials, suggesting that PIP2 exerts a tonic inhibitory influence. Our study, combining electrophysiological and direct binding assays, demonstrates that hEAG1 channels are subject to potent inhibitory modulation by multiple phospholipids and suggests that manipulations of the PIP2 signaling pathway may represent a strategy to treat hEAG1 channel-associated diseases.

Indexed as

Membrane PotentialsBinding SitesCalmodulinElectrophysiological PhenomenaEther-A-Go-Go Potassium ChannelsGene Expression RegulationHEK293 CellsHumansMicroscopy, ConfocalPhosphatidylinositol 4,5-DiphosphateProtein BindingSerotoninSignal TransductionSirolimusCalmodulinEther-A-Go-Go Potassium ChannelsKCNH1 protein, humanPhosphatidylinositol 4,5-DiphosphateSerotoninSirolimus

Identifiers

PMID27005320
PMCPMC4804213
OpenAlexW2312710769

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.