Evidence map›Paper›PMID 42248902›Full record

ArticleNature communications2026

Cryo-EM structures of heteromeric Kir4.1/5.1 channel suggest mechanisms of inward rectification and channel blockage.

Yingjie Ning, Xiaoyu Zhou, Yimin Zhang, Nanhao Chen, Qianbei Guo, Chenxia Gu, Didi Xu, Ran Cui, Jiayi Wang, Mengdan Li and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

15 authors.

Yingjie Ning *School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Xiaoyu Zhou *State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Yimin Zhang *Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Nanhao Chen *Center for Quantitative Biology, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China. nhchen@pku.edu.cn.
Qianbei Guo *State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Chenxia GuSchool of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Didi XuSchool of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Ran CuiSchool of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Jiayi WangSchool of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Mengdan LiState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Dongxue YangDepartment of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, China.ORCID http://orcid.org/0000-0001-7128-9831
Chen SongCenter for Quantitative Biology, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.ORCID http://orcid.org/0000-0001-9730-3216
Jie YuInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China. yujie@sioc.ac.cn.ORCID http://orcid.org/0000-0001-9227-038X
Zhaobing GaoState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. zbgao@simm.ac.cn.ORCID http://orcid.org/0000-0001-8931-5508
Jingpeng GeSchool of Life Science and Technology, ShanghaiTech University, Shanghai, China. gejp@shanghaitech.edu.cn.ORCID http://orcid.org/0000-0001-6164-1221

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Inwardly rectifying potassium (Kir) channels play key roles in regulating membrane potential and potassium transport through voltage-dependent inhibition by cytoplasmic Mg²⁺ and polyamines. Despite decades of extensive studies, the structural basis for polyamine-mediated inward rectification remains unclear. Here, we present cryo-EM structures of the heteromeric Kir4.1/5.1 channel-which is critical for brain and kidney function and whose dysfunction causes EAST/SeSAME syndrome-in its apo state and in complex with spermine, a channel blocker named VU0134992, and EHop-016, an inhibitor identified in this study. The structures of Kir4.1/5.1, in an opposite 2:2 heterotetrameric assembly, suggest an inner-ring blockage mechanism, where polyamines and channel blockers with different stoichiometries bind in a membrane-parallel orientation at the upper site of the transmembrane central cavity. Together with electrophysiology and molecular dynamics simulations, our findings provide mechanistic insights into inward rectification, channel inhibition, and the pharmacology of Kir channels.

Indexed as

Potassium Channels, Inwardly RectifyingAnimalsCryoelectron MicroscopyHEK293 CellsHumansKcnj10 ChannelMolecular Dynamics SimulationPotassiumPotassium Channel BlockersSpermineKcnj10 ChannelPotassiumPotassium Channel BlockersPotassium Channels, Inwardly RectifyingSpermine

Identifiers

PMID42248902
PMCPMC13396768

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.