Potassium sensing by renal distal tubules requires Kir4.1

Catherina A. Cuevas, Xiao Tong Su, Ming Xiao Wang, Andrew S. Terker, Dao Hong Lin, James (Jim) McCormick, Chao-Ling Yang, David Ellison, Wen Hui Wang

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The mammalian distal convoluted tubule (DCT) makes an important contribution to potassium homeostasis by modulating NaCl transport. The thiazide-sensitive Na+/Cl2 cotransporter (NCC) is activated by low potassium intake and by hypokalemia. Coupled with suppression of aldosterone secretion, activation of NCChelps to retain potassiumby increasing electroneutralNaCl reabsorption, therefore reducingNa+/K+ exchange. Yet the mechanisms bywhichDCT cells sense plasma potassiumconcentration and transmit the information to the apical membrane are not clear. Here, we tested the hypothesis that the potassium channel Kir4.1 is the potassium sensor of DCT cells.We generated mice in which Kir4.1 could be deleted in the kidney after themice are fully developed.Deletion of Kir4.1 in these mice led tomoderate saltwasting, low BP, and profound potassium wasting. Basolateral membranes of DCT cells were depolarized, nearly devoid of conductive potassium transport, and unresponsive to plasma potassium concentration. Although renalWNK4 abundance increased after Kir4.1 deletion, NCC abundance and function decreased, suggesting thatmembrane depolarization uncouplesWNK kinases fromNCC. Together, these results indicate thatKir4.1 mediates potassium sensing by DCT cells and couples this signal to apical transport processes.

Original languageEnglish (US)
Pages (from-to)1814-1825
Number of pages12
JournalJournal of the American Society of Nephrology
Volume28
Issue number6
DOIs
StatePublished - Jun 1 2017

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Distal Kidney Tubule
Potassium
Thiazides
Membranes
Hypokalemia
Potassium Channels
Plasma Cells
Aldosterone
Homeostasis
Phosphotransferases
Kidney

ASJC Scopus subject areas

  • Nephrology

Cite this

Cuevas, C. A., Su, X. T., Wang, M. X., Terker, A. S., Lin, D. H., McCormick, J. J., ... Wang, W. H. (2017). Potassium sensing by renal distal tubules requires Kir4.1. Journal of the American Society of Nephrology, 28(6), 1814-1825. https://doi.org/10.1681/ASN.2016090935

Potassium sensing by renal distal tubules requires Kir4.1. / Cuevas, Catherina A.; Su, Xiao Tong; Wang, Ming Xiao; Terker, Andrew S.; Lin, Dao Hong; McCormick, James (Jim); Yang, Chao-Ling; Ellison, David; Wang, Wen Hui.

In: Journal of the American Society of Nephrology, Vol. 28, No. 6, 01.06.2017, p. 1814-1825.

Research output: Contribution to journalArticle

Cuevas, Catherina A. ; Su, Xiao Tong ; Wang, Ming Xiao ; Terker, Andrew S. ; Lin, Dao Hong ; McCormick, James (Jim) ; Yang, Chao-Ling ; Ellison, David ; Wang, Wen Hui. / Potassium sensing by renal distal tubules requires Kir4.1. In: Journal of the American Society of Nephrology. 2017 ; Vol. 28, No. 6. pp. 1814-1825.
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