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. SUMMARY: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.
journal_name
Curr Opin Nephrol Hypertensjournal_title
Current opinion in nephrology and hypertensionauthors
Chen JC,Lin MX,Cheng CJdoi
10.1097/MNH.0000000000000683subject
Has Abstractpub_date
2021-03-01 00:00:00pages
166-172issue
2eissn
1062-4821issn
1473-6543pii
00041552-900000000-99013journal_volume
30pub_type
杂志文章abstract:PURPOSE OF REVIEW:In light of the recent changes to the kidney allocation system (KAS) and the observed increase in the rate of transplantation of the highly sensitized kidney transplant candidate, the evaluation and care of this population is a timely topic. RECENT FINDINGS:In its first year, the new KAS has already ...
journal_title:Current opinion in nephrology and hypertension
pub_type: 杂志文章,评审
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journal_title:Current opinion in nephrology and hypertension
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journal_title:Current opinion in nephrology and hypertension
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journal_title:Current opinion in nephrology and hypertension
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doi:10.1097/MNH.0b013e3282fd6e5b
更新日期:2008-07-01 00:00:00
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journal_title:Current opinion in nephrology and hypertension
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journal_title:Current opinion in nephrology and hypertension
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journal_title:Current opinion in nephrology and hypertension
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更新日期:2019-11-01 00:00:00
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journal_title:Current opinion in nephrology and hypertension
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journal_title:Current opinion in nephrology and hypertension
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journal_title:Current opinion in nephrology and hypertension
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更新日期:2009-03-01 00:00:00
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journal_title:Current opinion in nephrology and hypertension
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journal_title:Current opinion in nephrology and hypertension
pub_type: 杂志文章,评审
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更新日期:2012-09-01 00:00:00
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journal_title:Current opinion in nephrology and hypertension
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doi:10.1097/MNH.0b013e32832e316d
更新日期:2009-07-01 00:00:00
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journal_title:Current opinion in nephrology and hypertension
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journal_title:Current opinion in nephrology and hypertension
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doi:10.1097/MNH.0000000000000632
更新日期:2020-09-01 00:00:00
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journal_title:Current opinion in nephrology and hypertension
pub_type: 杂志文章,评审
doi:10.1097/01.mnh.0000222700.14960.18
更新日期:2006-05-01 00:00:00
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journal_title:Current opinion in nephrology and hypertension
pub_type: 杂志文章,评审
doi:10.1097/MNH.0b013e3281bd888d
更新日期:2007-07-01 00:00:00
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journal_title:Current opinion in nephrology and hypertension
pub_type: 杂志文章,评审
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更新日期:2011-11-01 00:00:00
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journal_title:Current opinion in nephrology and hypertension
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journal_title:Current opinion in nephrology and hypertension
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更新日期:2019-01-01 00:00:00
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journal_title:Current opinion in nephrology and hypertension
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journal_title:Current opinion in nephrology and hypertension
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journal_title:Current opinion in nephrology and hypertension
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更新日期:2012-01-01 00:00:00
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journal_title:Current opinion in nephrology and hypertension
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更新日期:2015-05-01 00:00:00
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journal_title:Current opinion in nephrology and hypertension
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更新日期:2010-07-01 00:00:00
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journal_title:Current opinion in nephrology and hypertension
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journal_title:Current opinion in nephrology and hypertension
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更新日期:2019-05-01 00:00:00
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journal_title:Current opinion in nephrology and hypertension
pub_type: 杂志文章,评审
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更新日期:2018-07-01 00:00:00
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journal_title:Current opinion in nephrology and hypertension
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更新日期:2016-11-01 00:00:00
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journal_title:Current opinion in nephrology and hypertension
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更新日期:2006-01-01 00:00:00