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During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.
Preparing your E-Poster
Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.
E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
Please follow the instructions below to input your abstract title.
Abstract titles should be brief and reflect the content of the abstract.
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 epithelial sodium channel (ENaC) activity via the mammalian target of rapamycin (mTOR)-dependent mechanisms, contributing to hypokalemia.
Metabolic cages, electrophysiology, immunoblotting, immunostaining, and in vivo diuretic response experiments were used to examine biochemical parameters, Kir4.1/Kir5.1 activity in the DCT, NCC and ENaC function under normal or K+ restriction conditions in the DCT-specific Kir4.1 knockout (DCT-Kir4.1 KO) mice.
DCT-Kir4.1 KO mice exhibited impaired basolateral K+ channel and NCC activity, with mild hypokalemia and metabolic alkalosis, highlighting that the DCT is a key site for Kir4.1 function. Amiloride treatment induced similar natriuresis and kaliuresis in DCT-Kir4.1 KO and kidney-specific Kir4.1 KO mice, but had minimal effects in collecting system Kir4.1 KO mice, suggesting enhanced ENaC activity following Kir4.1 deletion in the DCT. Notably, severe hypokalemia, along with upregulated ENaC expression and activity, was observed in DCT-Kir4.1 KO mice under dietary K+ restriction. Patch-clamp experiments further revealed elevated ENaC currents in the DCT2 of KO mice on a low-K+ diet, independent of aldosterone levels. Inhibition of mTOR with AZD8055 reduced SGK1/Nedd4-2 phosphorylation, cleaved α-ENaCexpression, and DCT2 ENaC currents, suggesting a role for mTOR in ENaC hyperactivity in K+-restricted DCT-Kir4.1 KO mice. This notion was also supported by observations that Rictor staining was significantly upregulated in the isolated DCT of these KO mice. Furthermore, the mTORC2 inhibitor JR-AB2-011 abolished elevated DCT2 ENaC currents in NPPB-treated isolated DCTs from both WT and KO mice.
We conclude that Kir4.1 deletion drives ENaC hyperactivity in the DCT via the Cl--dependent mTORC2/SGK1/Nedd4-2 signaling pathway, promoting low potassium diet-induced hypokalemia.
