Evidence map›Paper›PMID 35857840›Full record

ArticleScience advances2022

Electro-mechanical coupling of KCNQ channels is a target of epilepsy-associated mutations and retigabine.

Nien-Du Yang, Richard Kanyo, Lu Zhao, Jingru Li, Po Wei Kang, Alex Kelly Dou, Kelli McFarland White, Jingyi Shi, Jeanne M Nerbonne, Harley T Kurata and 1 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

11 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
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  3. Coupling of functionality to trafficking of KCNQ2/3 potassium channels at the axon initial segment.Proceedings of the National Academy of Sciences of the United States of America · 2026
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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

11 authors at 3 institutions in 2 countries.

Nien-Du YangDepartment of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, and Cardiac Bioelectricity and Arrhythmia Center, Washington University, St. Louis, MO 63130, USA.ORCID 0000-0002-5261-7382
Richard KanyoDepartment of Pharmacology, Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada.ORCID 0000-0002-8059-9628
Lu ZhaoDepartment of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, and Cardiac Bioelectricity and Arrhythmia Center, Washington University, St. Louis, MO 63130, USA.
Jingru LiDepartment of Pharmacology, Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada.ORCID 0000-0003-4027-1457
Po Wei KangDepartment of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, and Cardiac Bioelectricity and Arrhythmia Center, Washington University, St. Louis, MO 63130, USA.ORCID 0000-0002-5933-545X
Alex Kelly DouDepartment of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, and Cardiac Bioelectricity and Arrhythmia Center, Washington University, St. Louis, MO 63130, USA.ORCID 0000-0001-7446-1676
Kelli McFarland WhiteDepartment of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, and Cardiac Bioelectricity and Arrhythmia Center, Washington University, St. Louis, MO 63130, USA.ORCID 0000-0002-4626-5616
Jingyi ShiDepartment of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, and Cardiac Bioelectricity and Arrhythmia Center, Washington University, St. Louis, MO 63130, USA.
Jeanne M NerbonneDepartments of Developmental Biology and Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0001-8334-8499
Harley T KurataDepartment of Pharmacology, Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada.ORCID 0000-0003-4357-4189
Jianmin CuiDepartment of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, and Cardiac Bioelectricity and Arrhythmia Center, Washington University, St. Louis, MO 63130, USA.ORCID 0000-0002-9198-6332
Texas Cardiac Arrhythmia · USUniversity of Alberta · CAWashington University in St. Louis · US

Funding

MANIPULATING IKS AS A THERAPEUTIC APPROACH TO CARDIAC ARRHYTHMIASR01HL126774 · NHLBI · WASHINGTON UNIVERSITY · PI CUI, JIANMIN · 2015 to 2018
$3.1M
Molecular Determinants of Regional Differences in Human Ventricular Repolarization and RemodelingR01HL142520 · NHLBI · WASHINGTON UNIVERSITY · PI NERBONNE, JEANNE M. · 2019 to 2022
$1.6M
NEURONAL EXCITABILITY IN THE REGULATION OF CIRCADIAN RHYTHMSR01GM104991 · NIGMS · WASHINGTON UNIVERSITY · PI HERZOG, ERIK, NERBONNE, JEANNE M. · 2013 to 2016
$1.2M
NHLBI NIH HHS R01 HL126774NHLBI NIH HHS R01 HL142520NIGMS NIH HHS R01 GM104991
6 · The paper itself

Abstract

KCNQ2 and KCNQ3 form the M-channels that are important in regulating neuronal excitability. Inherited mutations that alter voltage-dependent gating of M-channels are associated with neonatal epilepsy. In the homolog KCNQ1 channel, two steps of voltage sensor activation lead to two functionally distinct open states, the intermediate-open (IO) and activated-open (AO), which define the gating, physiological, and pharmacological properties of KCNQ1. However, whether the M-channel shares the same mechanism is unclear. Here, we show that KCNQ2 and KCNQ3 feature only a single conductive AO state but with a conserved mechanism for the electro-mechanical (E-M) coupling between voltage sensor activation and pore opening. We identified some epilepsy-linked mutations in KCNQ2 and KCNQ3 that disrupt E-M coupling. The antiepileptic drug retigabine rescued KCNQ3 currents that were abolished by a mutation disrupting E-M coupling, suggesting that modulating the E-M coupling in KCNQ channels presents a potential strategy for antiepileptic therapy.

Identifiers

PMID35857840
PMCPMC9299555
OpenAlexW4285987564

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

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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.