Role of BK channels in hypertension and potassium secretion

J. David Holtzclaw, P. Richard Grimm, Steven C. Sansom

Research output: Contribution to journalReview article

45 Scopus citations

Abstract

Purpose of Review: This review summarizes recent studies of hypertension associated with a defect in renal K excretion due to genetic deletions of various components of the large, Ca-activated K channel (BK), and describes new evidence and theories regarding K secretory roles of BK in intercalated cells. Recent Findings: Isolated perfused tubule methods have revealed the importance of BK in flow-induced K secretion. Subsequently, mice with genetically deleted BK subunits revealed the complexities of BK-mediated K secretion. Deletion of BKα results in extreme aldosteronism, hypertension, and an absence of flow-induced K secretion. Deletion of the BKβ1 ancillary subunit results in decreased handling of a K load, increased plasma K, mild aldosteronism and hypertension that is exacerbated by a high K diet. Deletion of BKβ4 (β4KO) leads to insufficient K handling, high plasma K, fluid retention, but with milder hypertension. Fluid retention in β4KO may be the result of insufficient flow-induced secretion of adenosine triphosphate (ATP), which normally inhibits epithelial Na channels (ENaCs). Summary: Classical physiological analysis of electrolyte handling in knockout mice has enlightened our understanding of the mechanism of handling K loads by renal K channels. Studies have focused on the different roles of BK-α/β1 and BK-α/β4 in the kidney. BKβ1 hypertension may be a 'three-hit' hypertension, involving a K secretory defect, elevated production of aldosterone, and increased vascular tone. The disorders observed in BK knockout mice have shed new insights on the importance of proper renal K handling for maintaining volume balance and blood pressure.

Original languageEnglish (US)
Pages (from-to)512-517
Number of pages6
JournalCurrent opinion in nephrology and hypertension
Volume20
Issue number5
DOIs
StatePublished - Sep 2011

Keywords

  • BK channels
  • aldosterone
  • cortical collecting duct
  • intercalated cells
  • potassium

ASJC Scopus subject areas

  • Internal Medicine
  • Nephrology

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