Lack of Kir4.1 in the Distal Convoluted Tubule Causes <scp>ENaC</scp> Hyperactivity During K <sup>+</sup> Restriction Leading to Hypokalemia
AIM: Loss-of-function mutations in KCNJ10, encoding Kir4.1, cause EAST/SeSAME syndrome, with renal salt-wasting tubulopathy and hypokalemia. We hypothesized that Kir4.1 deletion specifically in the distal convoluted tubule (DCT) stimulates ENaC activity via the mammalian target of rapamycin (mTOR)-dependent mechanisms, contributing to hypokalemia. METHODS: restriction conditions. RESULTS: -restricted DCT-Kir4.1 KO mice. This notion was also supported by the upregulated Rictor expression observed in the isolated DCT of these KO mice. CONCLUSION: We conclude that Kir4.1 deletion drives ENaC hyperactivity in the DCT via the mTORC2-dependent SGK1/Nedd4-2 signaling pathway, promoting low potassium diet-induced hypokalemia.
Authors
- Fei-Hong Li
- Zhong‐Xiuzi Gao (ORCID: https://orcid.org/0009-0001-4170-1263)
- Ting‐Ting Shu
- Peng Wu (ORCID: https://orcid.org/0000-0002-9006-4977)
- Shaokang Pan (ORCID: https://orcid.org/0000-0002-8185-2525)
- Zi‐Hui Mao
- Zhangsuo Liu (ORCID: https://orcid.org/0000-0002-2916-8371)
- Yuanyuan Yang (ORCID: https://orcid.org/0000-0001-8606-079X)
- Ya-Fan Mu
- Rui-Juan Zhang
- Qing Zhang
- Dong‐Wei Liu
Institutions
- Zhengzhou University (CN)
- First Affiliated Hospital of Zhengzhou University (CN)
- Henan Provincial Center for Disease Control and Prevention (CN)
Publication Details
- Journal
- Acta Physiologica
- Published
- 2026-04-14
- DOI
- https://doi.org/10.1111/apha.70221
- Primary Topic
- Ion Transport and Channel Regulation
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Henan Province