NYMC Faculty Publications
Potassium Sensing by Renal Distal Tubules Requires Kir4.1
DOI
10.1681/ASN.2016090935
Journal Title
Journal of the American Society of Nephrology
First Page
1814
Last Page
1825
Document Type
Article
Publication Date
6-1-2017
Department
Pharmacology
Abstract
The mammalian distal convoluted tubule (DCT) makes an important contribution to potassium homeostasis by modulating NaCl transport. The thiazide-sensitive Na+./Cl- cotransporter (NCC) is activated by low potassium intake and by hypokalemia. Coupled with suppression of aldosterone secretion, activation of NCC helps to retain potassium by increasing electroneutral NaCl reabsorption, therefore reducing Na+./K+. exchange. Yet the mechanisms by which DCT cells sense plasma potassium concentration 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 the mice are fully developed. Deletion of Kir4.1 in these mice led to moderate salt wasting, 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 renal WNK4 abundance increased after Kir4.1 deletion, NCC abundance and function decreased, suggesting that membrane depolarization uncouples WNK kinases from NCC. Together, these results indicate that Kir4.1 mediates potassium sensing by DCT cells and couples this signal to apical transport processes.
Recommended Citation
Cuevas, C., Su, X., Wang, M., Terker, A., Lin, D., McCormick, J., Yang, C., Ellison, D., & Wang, W. (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