Role of BKβ1 in Na+ reabsorption by cortical collecting ducts of Na+-deprived mice

P. Richard Grimm, Debra L. Irsik, Liping Liu, J. David Holtzclaw, Steven C. Sansom

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Abstract

On a low-Na+ diet (LNa+), urinary Na+ loss is prevented by aldosteroneinduced Na+ reabsorption through epithelial Na+ channels (ENaC) in the connecting tubules (CNT) and cortical collecting ducts (CCD). However, the mechanism whereby K+ loss is minimized and Na+ reabsorption is maximized in the face of a reduced lumen-to-bath Na+ gradient is not fully understood. The large-conductance calciumactivated potassium channel (BK)β1 subunit (gene: Kcnmb1), which has a role in K+ secretion in the CNT, is absent in the CCD in mice on a control diet. We hypothesized that BKα/β1 helps to maximize Na+ reabsorption during Na+ deficiency. With LNa+, the Na+ clearance of Kcnmb1-mutant mice (Kcnmb1 -/-) was 45% greater and the plasma Na+ concentration and osmolality were significantly reduced compared with wild-type mouse (WT) controls. On LNa+, Kcnmb1-/- exhibited exacerbated volume depletion (higher Hct and weight loss) compared with WT. LNa+, which did not affect the mean arterial blood pressure (MAP) of WT, significantly reduced MAP of Kcnmb1-/-. The plasma aldosterone concentration of Kcnmb1-/- on LNa+ was significantly elevated compared with Kcnmb1-/- on a control diet but was not different from WT on LNa+. Immunohistochemical staining revealed that BKα and BKβ1, which were absent in the principal cells (PCs) of the CCD, were localized on the basolateral membrane (BSM) of PCs of WT on LNa+. Moreover, BKα was absent from the BSM of PCs of Na+-deficient Kcnmb1-/-. We conclude that part of the mechanism to maximize Na + reabsorption during Na+ deficiency is the placement of BKα/β1 channels in the BSM of CCD PCs.

Original languageEnglish (US)
Pages (from-to)F420-F428
JournalAmerican Journal of Physiology - Renal Physiology
Volume297
Issue number2
DOIs
Publication statusPublished - Aug 1 2009

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Keywords

  • Adrenal cortex
  • BK channel
  • Maxi K
  • Mineralocorticoids
  • Potassium secretion

ASJC Scopus subject areas

  • Physiology
  • Urology

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