The ClC-K2 chloride channel is critical for salt handling in the distal nephron

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Item Type:	Article
Title:	The ClC-K2 chloride channel is critical for salt handling in the distal nephron
Creators Name:	Hennings, J.C., Andrini, O., Picard, N., Paulais, M., Huebner, A.K., Lopez Cayuqueo, I.K., Bignon, Y., Keck, M., Cornière, N., Böhm, D., Jentsch, T.J., Chambrey, R., Teulon, J., Hübner, C.A. and Eladari, D.
Abstract:	Chloride transport by the renal tubule is critical for blood pressure (BP), acid-base, and potassium homeostasis. Chloride uptake from the urinary fluid is mediated by various apical transporters, whereas basolateral chloride exit is thought to be mediated by ClC-Ka/K1 and ClC-Kb/K2, two chloride channels from the ClC family, or by KCl cotransporters from the SLC12 gene family. Nevertheless, the localization and role of ClC-K channels is not fully resolved. Because inactivating mutations in ClC-Kb/K2 cause Bartter syndrome, a disease that mimics the effects of the loop diuretic furosemide, ClC-Kb/K2 is assumed to have a critical role in salt handling by the thick ascending limb. To dissect the role of this channel in detail, we generated a mouse model with a targeted disruption of the murine ortholog ClC-K2. Mutant mice developed a Bartter syndrome phenotype, characterized by renal salt loss, marked hypokalemia, and metabolic alkalosis. Patch-clamp analysis of tubules isolated from knockout (KO) mice suggested that ClC-K2 is the main basolateral chloride channel in the thick ascending limb and in the aldosterone-sensitive distal nephron. Accordingly, ClC-K2 KO mice did not exhibit the natriuretic response to furosemide and exhibited a severely blunted response to thiazide. We conclude that ClC-Kb/K2 is critical for salt absorption not only by the thick ascending limb, but also by the distal convoluted tubule.
Keywords:	Chloride Channels, Bartter-s Syndrome, Ion Transport, Transgenic Mouse, Animals, Mice
Source:	Journal of the American Society of Nephrology
ISSN:	1046-6673
Publisher:	American Society of Nephrology
Volume:	28
Number:	1
Page Range:	209-217
Date:	January 2017
Official Publication:	https://doi.org/10.1681/ASN.2016010085
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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