Journal article
WNK4 kinase: role of chloride sensing in the distal convoluted tubule
Current opinion in nephrology and hypertension, Vol.30(2), pp.166-172
03/01/2021
DOI: 10.1097/MNH.0000000000000683
PMID: 33394730
Abstract
Purpose of review This review focuses on recent efforts in identifying with-no-lysine kinase 4 (WNK4) as a physiological intracellular chloride sensor and exploring regulators of intracellular chloride concentration ([Cl-]i) in the distal convoluted tubule (DCT). Recent findings The discovery of WNK1's chloride-binding site provides the mechanistic details of the chloride-sensing regulation of WNK kinases. The subsequent in-vitro studies reveal that the chloride sensitivities of WNK kinases were variable. Because of its highest chloride sensitivity and dominant expression, WNK4 emerges as the leading candidate of the chloride sensor in DCT. The presentation of hypertension and increased sodium-chloride cotransporter (NCC) activity in chloride-insensitive WNK4 mice proved that WNK4 is inhibitable by physiological [Cl-]i in DCT. The chloride-mediated WNK4 regulation is responsible for hypokalemia-induced NCC activation but unnecessary for hyperkalemia-induced NCC deactivation. This chloride-sensing mechanism requires basolateral potassium and chloride channels or cotransporters, including Kir4.1/5.1, ClC-Kb, and possibly KCCs, to modulate [Cl-]i in response to the changes of plasma potassium. WNK4 is both a master NCC stimulator and an in-vivo chloride sensor in DCT. The understanding of chloride-mediated regulation of WNK4 explains the inverse relationship between dietary potassium intake and NCC activity.
Details
- Title: Subtitle
- WNK4 kinase: role of chloride sensing in the distal convoluted tubule
- Creators
- Jen-Chi Chen - Tri-Service General HospitalMeng-Xuan Lin - Tri-Service General HospitalChih-Jen Cheng - Tri-Service General Hospital
- Resource Type
- Journal article
- Publication Details
- Current opinion in nephrology and hypertension, Vol.30(2), pp.166-172
- Publisher
- Lippincott Williams & Wilkins
- DOI
- 10.1097/MNH.0000000000000683
- PMID
- 33394730
- ISSN
- 1062-4821
- eISSN
- 1473-6543
- Number of pages
- 7
- Grant note
- MOST107-2314-B-016-010-MY3; TSGH-C108-133; TSGH-D-109124 / Ministry of Science and Technology and Tri-Service General Hospital in Taiwan
- Language
- English
- Date published
- 03/01/2021
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984383295602771
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