Role of WNK4 and kidney-specific WNK1 in mediating the effect of high dietary K+ intake on ROMK channel in the distal convoluted tubule

Peng Wu, Zhong Xiuzi Gao, Xiao Tong Su, David H. Ellison, Juliette Hadchouel, Jacques Teulon, Wen Hui Wang

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


With-no-lysine kinase 4 (WNK4) and kidney-specific (KS)-WNK1 regulate ROMK (Kir1.1) channels in a variety of cell models. We now explore the role of WNK4 and KS-WNK1 in regulating ROMK in the native distal convoluted tubule (DCT)/connecting tubule (CNT) by measuring tertiapin-Q (TPNQ; ROMK inhibitor)-sensitive K+ currents with whole cell recording. TPNQ-sensitive K+ currents in DCT2/CNT of KS-WNK1-/- and WNK4-/- mice were significantly smaller than that of WT mice. In contrast, the basolateral K+ channels (a Kir4.1/5.1 heterotetramer) in the DCT were not inhibited. Moreover, WNK4-/- mice were hypokalemic, while KS-WNK1-/- mice had normal plasma K+ levels. High K+ (HK) intake significantly increased TPNQ-sensitive K+ currents in DCT2/CNT of WT and WNK4-/- mice but not in KS-WNK1-/- mice. However, TPNQ-sensitive K+ currents in the cortical collecting duct (CCD) were normal not only under control conditions but also significantly increased in response to HK in KS-WNK1-/- mice. This suggests that the deletion of KS-WNK1-induced inhibition of ROMK occurs only in the DCT2/CNT. Renal clearance study further demonstrated that the deletion of KS-WNK1 did not affect the renal ability of K+ excretion under control conditions and during increasing K+ intake. Also, HK intake did not cause hyperkalemia in KS-WNK1-/- mice. We conclude that KS-WNK1 but not WNK4 is required for HK intake-induced stimulation of ROMK activity in DCT2/CNT. However, KS-WNK1 is not essential for HK-induced stimulation of ROMK in the CCD, and the lack of KS-WNK1 does not affect net renal K+ excretion.

Original languageEnglish (US)
Pages (from-to)F223-F230
JournalAmerican Journal of Physiology - Renal Physiology
Issue number2
StatePublished - Aug 2018


  • Hyperkalemia
  • Hypokalemia
  • K excretion
  • Kir1.1
  • Kir4.1

ASJC Scopus subject areas

  • Physiology
  • Urology


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