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Record W4416694269 · doi:10.1093/bbb/zbaf175

Inhibition of potassium chloride cotransporters impairs muscle contraction and induces atrophy in C2C12 myotubes

2025· article· en· W4416694269 on OpenAlexaff
Haruka Kimura, Makoto Shimizu, Yu Takahashi, Yoshio Yamauchi, Ryuichiro Sato, Takashi Sasaki

Bibliographic record

VenueBioscience Biotechnology and Biochemistry · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicIon Transport and Channel Regulation
Canadian institutionsNutrasource
FundersJapan Society for the Promotion of ScienceLotte Foundation
KeywordsMyogenesisSkeletal muscleC2C12MyocyteMuscle atrophyCotransporterIntracellularExtracellularMuscle contraction

Abstract

fetched live from OpenAlex

In skeletal muscle cells, the resting membrane potential is primarily determined by Cl-, necessitating precise regulation of intracellular and extracellular Cl- balance. Potassium chloride cotransporters (KCCs), members of the cation-chloride cotransporter superfamily, facilitate the efflux of K+ and Cl- at a 1:1 ratio. However, the specific roles of KCCs in skeletal muscle remain poorly understood. In this study, we investigated the function of KCCs in skeletal muscle cells using [(dihydroindenyl)oxy]acetic acid (DIOA), a KCCs inhibitor. DIOA treatment of cultured C2C12 myotubes impaired contractility in response to electrical pulse stimulation. Additionally, DIOA-treated myotubes exhibited muscle atrophy, accompanied by increased expression of atrogenes such as Atrogin-1 and MuRF1. These findings reveal a novel role for KCCs in skeletal muscle and provide insights that may contribute to the development of preventive or therapeutic strategies for muscle disorders and atrophy.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.043
Threshold uncertainty score0.467

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.004
GPT teacher head0.211
Teacher spread0.207 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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