title: Role of BK channels in hypertension and potassium secretion.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5850, USA.
authors.forename: J David
authors.initials: JD
authors.lastname: Holtzclaw
authors.forename: P Richard
authors.initials: PR
authors.lastname: Grimm
authors.forename: Steven C
authors.initials: SC
authors.lastname: Sansom
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D017136:Ion Transport; D007684:Kidney Tubules / Q000378:metabolism* / Q000503:physiopathology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011188:Potassium / Q000097:blood / Q000378:metabolism*; D014882:Water-Electrolyte Balance
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D000450:Aldosterone; D011188:Potassium