title: Relation between BK-α/β4-mediated potassium secretion and ENaC-mediated sodium reabsorption.
abstract: The large-conductance, calcium-activated BK-α/β4 potassium channel, localized to the intercalated cells of the distal nephron, mediates potassium secretion during high-potassium, alkaline diets. Here we determine whether BK-α/β4-mediated potassium transport is dependent on epithelial sodium channel (ENaC)-mediated sodium reabsorption. We maximized sodium-potassium exchange in the distal nephron by feeding mice a low-sodium, high-potassium diet. Wild-type and BK-β4 knockout mice were maintained on a low-sodium, high-potassium, alkaline diet or a low-sodium, high-potassium, acidic diet for 7-10 days. Wild-type mice maintained potassium homeostasis on the alkaline, but not acid, diet. BK-β4 knockout mice could not maintain potassium homeostasis on either diet. During the last 12 h of diet, wild-type mice on either a regular, alkaline, or an acid diet, or knockout mice on an alkaline diet, were administered amiloride (an ENaC inhibitor). Amiloride enhanced sodium excretion in all wild-type and knockout groups to similar values; however, amiloride diminished potassium excretion by 59% in wild-type but only by 33% in knockout mice on an alkaline diet. Similarly, amiloride decreased the trans-tubular potassium gradient by 68% in wild-type but only by 42% in knockout mice on an alkaline diet. Amiloride treatment equally enhanced sodium excretion and diminished potassium secretion in knockout mice on an alkaline diet and wild-type mice on an acid diet. Thus, the enhanced effect of amiloride on potassium secretion in wild-type compared to knockout mice on the alkaline diet clarify a BK- α/β4-mediated potassium secretory pathway in intercalated cells driven by ENaC-mediated sodium reabsorption linked to bicarbonate secretion.
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Donghai
authors.initials: D
authors.lastname: Wen
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Cornelius
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Dianelys
authors.initials: D
authors.lastname: Rivero-Hernandez
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Huaqing
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Weinstein
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Sansom
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D062686:Epithelial Sodium Channel Blockers / Q000494:pharmacology; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006852:Hydrochlorothiazide / Q000494:pharmacology; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009399:Nephrons / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D017419:Potassium, Dietary / Q000008:administration & dosage; D012964:Sodium / Q000378:metabolism*; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology; D012982:Sodium, Dietary / Q000008:administration & dosage
chemical_list: D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D017419:Potassium, Dietary; D049993:Sodium Chloride Symporter Inhibitors; D012982:Sodium, Dietary; D006852:Hydrochlorothiazide; D000584:Amiloride; D012964:Sodium; D011188:Potassium