title: Bicarbonate promotes BK-α/β4-mediated K excretion in the renal distal nephron.
abstract: Ca-activated K channels (BK), which are stimulated by high distal nephron flow, are utilized during high-K conditions to remove excess K. Because BK predominantly reside with BK-β4 in acid/base-transporting intercalated cells (IC), we determined whether BK-β4 knockout mice (β4KO) exhibit deficient K excretion when consuming a high-K alkaline diet (HK-alk) vs. high-K chloride diet (HK-Cl). When wild type (WT) were placed on HK-alk, but not HK-Cl, renal BK-β4 expression increased (Western blot). When WT and β4KO were placed on HK-Cl, plasma K concentration ([K]) was elevated compared with control K diets; however, K excretion was not different between WT and β4KO. When HK-alk was consumed, the plasma [K] was lower and K clearance was greater in WT compared with β4KO. The urine was alkaline in mice on HK-alk; however, urinary pH was not different between WT and β4KO. Immunohistochemical analysis of pendrin and V-ATPase revealed the same increases in β-IC, comparing WT and β4KO on HK-alk. We found an amiloride-sensitive reduction in Na excretion in β4KO, compared with WT, on HK-alk, indicating enhanced Na reabsorption as a compensatory mechanism to secrete K. Treating mice with an alkaline, Na-deficient, high-K diet (LNaHK) to minimize Na reabsorption exaggerated the defective K handling of β4KO. When WT on LNaHK were given NH(4)Cl in the drinking water, K excretion was reduced to the magnitude of β4KO on LNaHK. These results show that WT, but not β4KO, efficiently excretes K on HK-alk but not on HK-Cl and suggest that BK-α/β4-mediated K secretion is promoted by bicarbonaturia.
authors.affiliation: Dept. of Cellular and Integrative Physiology, Nebraska Medical Center, Omaha, NE 68198-5850, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Cornelius
authors.forename: Donghai
authors.initials: D
authors.lastname: Wen
authors.forename: Lori I
authors.initials: LI
authors.lastname: Hatcher
authors.forename: Steven C
authors.initials: SC
authors.lastname: Sansom
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology*; D053503:Epithelial Sodium Channels / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / 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; D023421:Models, Animal; D009399:Nephrons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D017419:Potassium, Dietary / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism
chemical_list: D001639:Bicarbonates; 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; D011189:Potassium Chloride; D012964:Sodium; D011188:Potassium