Bicarbonate promotes BK-α/β4-mediated K excretion in the renal distal nephron

Ryan J. Cornelius, Donghai Wen, Lori I. Hatcher, Steven C. Sansom

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 amiloridesensitive 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 NH4Cl 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.

Original languageEnglish (US)
Pages (from-to)F1563-F1571
JournalAmerican Journal of Physiology - Renal Physiology
Volume303
Issue number11
DOIs
StatePublished - Dec 1 2012

Fingerprint

Nephrons
Bicarbonates
Knockout Mice
Diet
Chlorides
Renal Elimination
Large-Conductance Calcium-Activated Potassium Channels
Drinking Water
Adenosine Triphosphatases
Western Blotting

Keywords

  • Acidosis
  • Alkalosis
  • Collecting duct
  • Distal nephron
  • Intercalated cells
  • Maxi K
  • Potassium secretion

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Bicarbonate promotes BK-α/β4-mediated K excretion in the renal distal nephron. / Cornelius, Ryan J.; Wen, Donghai; Hatcher, Lori I.; Sansom, Steven C.

In: American Journal of Physiology - Renal Physiology, Vol. 303, No. 11, 01.12.2012, p. F1563-F1571.

Research output: Contribution to journalArticle

Cornelius, Ryan J. ; Wen, Donghai ; Hatcher, Lori I. ; Sansom, Steven C. / Bicarbonate promotes BK-α/β4-mediated K excretion in the renal distal nephron. In: American Journal of Physiology - Renal Physiology. 2012 ; Vol. 303, No. 11. pp. F1563-F1571.
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AB - 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 amiloridesensitive 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 NH4Cl 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.

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KW - Intercalated cells

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