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Potassium chloride cotransporters (KCCs), members of the cation-chloride cotransporter superfamily, facilitate the efflux of K+ and Cl\u2212 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.<\/jats:p>","DOI":"10.1093\/bbb\/zbaf175","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T13:21:37Z","timestamp":1764163297000},"page":"206-213","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of potassium chloride cotransporters impairs muscle contraction and induces atrophy in C2C12 myotubes"],"prefix":"10.1093","volume":"90","author":[{"given":"Haruka","family":"Kimura","sequence":"first","affiliation":[{"name":"Graduate School of Agricultural and Life Sciences, The University of Tokyo Nutri-Life Science Laboratory, Department of Applied Biological Chemistry, , Tokyo 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