Furosemide reduces BK-αβ4-mediated K+ secretion in mice on an alkaline high-K+ diet

Bangchen Wang, Jun Wang-France, Huaqing Li, Steven C. Sansom

Research output: Contribution to journalArticle

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Abstract

Special high-K diets have cardioprotective effects and are often warranted in conjunction with diuretics such as furosemide for treating hypertension. However, it is not understood how a high-K diet (HK) influences the actions of diuretics on renal K+ handling. Furosemide acidifies the urine by increasing acid secretion via the Na+-H+ exchanger 3 (NHE3) in TAL and vacuolar H+-ATPase (V-ATPase) in the distal nephron. We previously found that an alkaline urine is required for large conductance Ca2+-activated K+ (BK)-αβ4-mediated K+ secretion in mice on HK. We therefore hypothesized that furosemide could reduce BK-αβ4-mediated K+ secretion by acidifying the urine. Treating with furosemide (drinking water) for 11 days led to decreased urine pH in both wild-type (WT) and BK-β4-knockout mice (BK-β4-KO) with increased V-ATPase expression and elevated plasma aldosterone levels. However, furosemide decreased renal K+ clearance and elevated plasma [K+] in WT but not BK-β4-KO. Western blotting and immunofluorescence staining showed that furosemide treatment decreased cortical expression of BK-β4 and reduced apical localization of BK-α in connecting tubules. Addition of the carbonic anhydrase inhibitor, acetazolamide, to furosemide water restored urine pH along with renal K+ clearance and plasma [K+] to control levels. Acetazolamide plus furosemide also restored the cortical expression of BK-β4 and BK-α in connecting tubules. These results indicate that in mice adapted to HK, furosemide reduces BK-αβ4-mediated K+ secretion by acidifying the urine.

Original languageEnglish (US)
Pages (from-to)F341-F350
JournalAmerican journal of physiology. Renal physiology
Volume316
Issue number2
DOIs
StatePublished - Feb 1 2019

Fingerprint

Furosemide
Diet
Urine
Vacuolar Proton-Translocating ATPases
Acetazolamide
Kidney
Diuretics
Knockout Mice
Carbonic Anhydrase Inhibitors
Sodium-Hydrogen Antiporter
Nephrons
Aldosterone
Drinking Water
Fluorescent Antibody Technique
Western Blotting
Staining and Labeling
Hypertension
Acids
Water

Keywords

  • furosemide
  • high-K diet
  • large conductance Ca-activated K
  • urine pH

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Furosemide reduces BK-αβ4-mediated K+ secretion in mice on an alkaline high-K+ diet. / Wang, Bangchen; Wang-France, Jun; Li, Huaqing; Sansom, Steven C.

In: American journal of physiology. Renal physiology, Vol. 316, No. 2, 01.02.2019, p. F341-F350.

Research output: Contribution to journalArticle

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