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

Chih Jen Cheng, Michel Baum, Chou Long Huang

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)F397-F402
JournalAmerican Journal of Physiology - Renal Physiology
Volume304
Issue number4
DOIs
StatePublished - Feb 15 2013

Keywords

  • Cortical collecting duct
  • In vitro microperfusion
  • Kidney-specific WNK1
  • WNK kinase

ASJC Scopus subject areas

  • Physiology
  • Urology

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