Evidence map›Paper›PMID 41711638›Full record

ArticleThe Journal of general physiology2026

Structure-function analysis of the lithium-ion selectivity of the voltage-gated sodium channel.

Yuki K Maeda, Kentaro Kojima, Tomoe Y Nakamura, Toru Nakatsu, Katsumasa Irie

Abstract read
In one paragraph

Article in The Journal of general physiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Yuki K MaedaDepartment of Pharmacology, Faculty of Medicine, Wakayama Medical University, Wakayama, Japan.ORCID 0009-0002-8168-8646
Kentaro KojimaDepartment of Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.ORCID 0009-0000-5227-4175
Tomoe Y NakamuraDepartment of Pharmacology, Faculty of Medicine, Wakayama Medical University, Wakayama, Japan.ORCID 0000-0003-0086-1022
Toru NakatsuDepartment of Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.ORCID 0000-0002-9582-4023
Katsumasa IrieDepartment of Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.ORCID 0000-0002-8178-1552

Funding

Grants-in-Aid for Scientific Research 17K17795Grants-in-Aid for Scientific Research 20K09193Grants-in-Aid for Scientific Research 24K02168Institute for Fermentation G-2021-2-020Japan Agency for Medical Research and Development JP22ama121001Japan Agency for Medical Research and Development JP23ama121001Salt Science Research Foundation 202403SEI Group CSR FoundationTakeda Science Found
6 · The paper itself

Abstract

Voltage-gated sodium channels (Navs) selectively conduct Na+ to generate action potentials. Na+ permeates Navs with significantly higher efficiency than many other cations, but Li+ can also permeate Navs to an extent comparable with Na+. Li+ in the blood is known to enter cells via Navs and to have a beneficial effect on various neuropathies. However, the molecular basis of the high Li+ selectivity of Navs was unclear. In this study, using a prokaryotic Nav, we successfully created the first Nav mutant to be more selective for Li+ than for Na+. Electrophysiological and crystallographic analyses suggested the critical determinants of high Li+ selectivity: the strong electrostatic interaction between the ion pathway and hydrated ions, and the smaller number of hydration water exchanges within the ion pathway. Additionally, the extensive interactions around the ion pathway were shown to support monovalent cation selectivity. New drug directions based on the molecular basis for Li+ permeation may target various neurological disorders and could clarify the broader biological effects of lithium.

Indexed as

LithiumSodium ChannelsAnimalsIon Channel GatingMutationSodiumStructure-Activity RelationshipLithiumSodiumSodium Channels

Identifiers

PMID41711638
PMCPMC12919392

What Socratic holds

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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.