L-WNK1 is required for BK channel activation in intercalated cells

Evan C. Ray, Rolando Carrisoza-Gaytan, Mohammad Al-Bataineh, Allison L. Marciszyn, Lubika J. Nkashama, Jingxin Chen, Aaliyah Winfrey, Shawn Griffiths, Tracey R. Lam, Daniel Flores, Peng Wu, Wen Hui Wang, Chou Long Huang, Arohan R. Subramanya, Thomas R. Kleyman, Lisa M. Satlin

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Large-conductance Kþ (BK) channels expressed in intercalated cells (ICs) in the aldosterone-sensitive distal nephron (ASDN) mediate flow-induced Kþ secretion. In the ASDN of mice and rabbits, IC BK channel expression and activity increase with a high-Kþ diet. In cell culture, the long isoform of with-no-lysine kinase 1 (L-WNK1) increases BK channel expression and activity. Apical L-WNK1 expression is selectively enhanced in ICs in the ASDN of rabbits on a high-Kþ diet, suggesting that L-WNK1 contributes to BK channel regulation by dietary Kþ. We examined the role of IC L-WNK1 expression in enhancing BK channel activity in response to a high-Kþ diet. Mice with IC-selective deletion of L-WNK1 (IC-L-WNK1-KO) and littermate control mice were placed on a high-Kþ (5% Kþ, as KCl) diet for 10 or more days. IC-L-WNK1-KO mice exhibited reduced IC apical þ subapical a-subunit expression and BK channel-dependent whole cell currents compared with controls. Six-hour urinary Kþ excretion in response a saline load was similar in IC-L-WNK1-KO mice and controls. The observations that IC-L-WNK1-KO mice on a high-Kþ diet have higher blood Kþ concentration and reduced IC BK channel activity are consistent with impaired urinary Kþ secretion, demonstrating that IC L-WNK1 has a role in the renal adaptation to a high-Kþ diet. NEW & NOTEWORTHY When mice are placed on a high-Kþ diet, genetic disruption of the long form of with no lysine kinase 1 (L-WNK1) in intercalated cells reduced relative apical þ subapical localization of the large-conductance Kþ channel, blunted large-conductance Kþ channel currents in intercalated cells, and increased blood Kþ concentration. These data confirm an in vivo role of L-WNK1 in intercalated cells in adaptation to a high-Kþ diet.

Original languageEnglish (US)
Pages (from-to)F245-F254
JournalAmerican Journal of Physiology - Renal Physiology
Volume321
Issue number2
DOIs
StatePublished - Aug 2021
Externally publishedYes

Keywords

  • Intercalated cells
  • Large-conductance potassium channel
  • Potassium secretion
  • WNK1 kinase

ASJC Scopus subject areas

  • Physiology
  • Urology

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