Journal article
Kidney-specific WNK1 inhibits sodium reabsorption in the cortical thick ascending limb
American journal of physiology. Renal physiology, Vol.303(5), pp.F667-F673
07/11/2012
DOI: 10.1152/ajprenal.00290.2012
PMCID: PMC3468497
PMID: 22791335
Abstract
Kidney-specific WNK1 (KS-WNK1) is a variant of full-length WNK1. Previous studies have reported that KS-WNK1 is predominantly expressed in the distal convoluted tubule (DCT) where it regulates sodium-chloride cotransporter. The role of KS-WNK1 in other nephron segments is less clear. Here, we measured the expression of KS-WNK1 transcript in microdissected renal tubules and found that KS-WNK1 was most abundant in the DCT, followed by cortical thick ascending limb (cTAL), connecting tubule, and cortical collecting duct. A high K
+
diet enhanced the expression of KS-WNK1 in the DCT and cTAL, selectively. It has been reported that a high-K diet suppresses Na
+
reabsorption in TAL. To understand the role of KS-WNK1 in Na
+
transport in cTAL and the regulation by dietary K
+
, we examined Na
+
reabsorption using in vitro microperfusion in cTAL isolated from KS-WNK1-knockout mice and wild-type littermates fed either a control-K
+
or high-K
+
diet. Furosemide-sensitive Na
+
reabsorption in cTAL was higher in KS-WNK1-knockout (KO) mice than in wild-type. A high-K
+
diet inhibited Na
+
reabsorption in cTAL from wild-type mice, but the inhibition was eliminated in KS-WNK1-KO mice. We further examined the role of KS-WNK1 using transgenic mice that overexpress KS-WNK1. Na
+
reabsorption in cTAL was lower in transgenic than in wild-type mice. In whole animal clearance studies, a high-K
+
diet increased daily urine volume and urinary Na
+
and K
+
excretion in wild-type mice, which was blunted in KS-WNK1-KO mice. Thus KS-WNK1 inhibits Na
+
reabsorption in cTAL and mediates the inhibition of Na
+
reabsorption in the segment by a high-K diet.
Details
- Title: Subtitle
- Kidney-specific WNK1 inhibits sodium reabsorption in the cortical thick ascending limb
- Creators
- Chih-Jen Cheng - The University of Texas Southwestern Medical CenterThao Truong - The University of Texas Southwestern Medical CenterMichel Baum - NeurologyChou-Long Huang - The University of Texas Southwestern Medical Center
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Renal physiology, Vol.303(5), pp.F667-F673
- Publisher
- American Physiological Society
- DOI
- 10.1152/ajprenal.00290.2012
- PMID
- 22791335
- PMCID
- PMC3468497
- ISSN
- 1931-857X
- eISSN
- 1522-1466
- Language
- English
- Date published
- 07/11/2012
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984359675502771
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