Regulation of BK-α expression in the distal nephron by aldosterone and urine pH

Donghai Wen, Ryan J. Cornelius, Yang Yuan, Steven C. Sansom

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

In the distal nephron, the large-conductance Ca-activated K (BK) channel, comprised of a pore-forming- α (BK- α) and the BK-β4 subunit, promotes K excretion when mice are maintained on a high-K alkaline diet (HK-alk). We examined whether BK-β4 and the acid-base status regulate apical membrane expression of BK- in the cortical (CCD) and medullary collecting ducts (MCD) using immunohistochemical analysis (IHC) and Western blot. With the use of IHC, BK- of mice on acontrol diet localized mostly cytoplasmically in intercalated cells (IC) of the CCD and in the perinuclear region of both principle cells (PC) and IC of the MCD. HK-alk wild-type mice (WT), but not BK- β 4 knockout mice (β 4KO), exhibited increased apical BK- α in both the CCD and MCD. When given a high-K acidic diet (HK-Cl), BK- expression increased but remained cytoplasmic in the CCD and perinuclear in the MCD of both WT and β 4KO. Western blot confirmed that total BK- α expression was enhanced by either HK-alk or HK-Cl but only increased in the plasma membrane with HK-alk. Compared with controls, mice drinking NaHCO3 water exhibited more apical BK- α and total cellular BK- β 4. Spironolactone given to mice on HK-alk significantly reduced K secretion and decreased total cellular BK- α but did not affect cellular BK- β 4 and apical BK- α. Experiments with MDCK-C11 cells indicated that BK- β 4 stabilizes surface BK- α by inhibiting degradation through a lysosomal pathway. These data suggest that aldosterone mediates a high-K-induced increase in BK- α and urinary alkalinization increases BK- β 4 expression, which promotes the apical localization of BK- α.

Original languageEnglish (US)
Pages (from-to)F463-F476
JournalAmerican Journal of Physiology - Renal Physiology
Volume305
Issue number4
DOIs
StatePublished - May 8 2013

Keywords

  • Acid/base
  • Apical membrane
  • Intercalated cells
  • Maxi K
  • Potassium secretion

ASJC Scopus subject areas

  • Physiology
  • Urology

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