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Kidney-specific WNK1 regulates sodium reabsorption and potassium secretion in mouse cortical collecting duct
Journal article   Open access   Peer reviewed

Kidney-specific WNK1 regulates sodium reabsorption and potassium secretion in mouse cortical collecting duct

Chih-Jen Cheng, Michel Baum and Chou-Long Huang
American journal of physiology. Renal physiology, Vol.304(4), pp.F397-402
02/15/2013
DOI: 10.1152/ajprenal.00589.2012
PMCID: PMC3566501
PMID: 23195681
url
https://doi.org/10.1152/ajprenal.00589.2012View
Published (Version of record) Open Access

Abstract

Kidney-specific with-no-lysine kinase 1 (KS-WNK1) is a kinase-deficient variant of WNK1 that is expressed exclusively in the kidney. It is abundantly expressed in the distal convoluted tubule (DCT) and to a lesser extent in the cortical thick ascending limb (cTAL), connecting tubule, and cortical collecting duct (CCD). KS-WNK1 inhibits Na(+)-K(+)-2Cl(-)- and sodium chloride cotransporter-mediated Na(+) reabsorption in cTAL and DCT, respectively. Here, we investigated the role of KS-WNK1 in regulating Na(+) and K(+) transport in CCD using in vitro microperfusion of tubules isolated from KS-WNK1 knockout mice and control wild-type littermates. Because baseline K(+) secretion and Na(+) reabsorption were negligible in mouse CCD, we studied tubules isolated from mice fed a high-K(+) diet for 2 wk. Compared with that in wild-type tubules, K(+) secretion was reduced in KS-WNK1 knockout CCD perfused at a low luminal fluid rate of ~1.5 nl/min. Na(+) reabsorption and the lumen-negative transepithelial potential difference were also lower in the KS-WNK1 knockout CCD compared with control CCD. Increasing the perfusion rate to ~5.5 nl/min stimulated K(+) secretion in the wild-type as well as knockout CCD. The magnitudes of flow-stimulated increase in K(+) secretion were similar in wild-type and knockout CCD. Maxi-K(+) channel inhibitor iberiotoxin had no effect on K(+) secretion when tubules were perfused at ~1.5 nl/min, but completely abrogated the flow-dependent increase in K(+) secretion at ~5.5 nl/min. These findings support the notion that KS-WNK1 stimulates ROMK-mediated K(+) secretion, but not flow-dependent K(+) secretion mediated by maxi-K(+) channels in CCD. In addition, KS-WNK1 plays a role in regulating Na(+) transport in the CCD.
 Potassium - metabolism Absorption - physiology Sequence Deletion Membrane Potentials - genetics Exons Minor Histocompatibility Antigens Male Potassium, Dietary - administration & dosage Large-Conductance Calcium-Activated Potassium Channels - antagonists & inhibitors Sodium - metabolism Kidney Tubules, Collecting - secretion WNK Lysine-Deficient Protein Kinase 1 Absorption - genetics Female Kidney Tubules, Collecting - drug effects Membrane Potentials - drug effects Protein-Serine-Threonine Kinases - physiology Tissue Culture Techniques Protein-Serine-Threonine Kinases - genetics Membrane Potentials - physiology Mice, Knockout Peptides - pharmacology Kidney Tubules, Collecting - metabolism Animals Kidney Tubules, Distal - drug effects Perfusion Potassium Channels, Inwardly Rectifying - physiology Absorption - drug effects Mice Kidney Tubules, Distal - metabolism

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