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Bicarbonate promotes BK-α/β4-mediated K excretion in the renal distal nephron
- Source :
- American Journal of Physiology-Renal Physiology. 303:F1563-F1571
- Publication Year :
- 2012
- Publisher :
- American Physiological Society, 2012.
-
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 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.
- Subjects :
- Epithelial sodium channel
medicine.medical_specialty
Alkalosis
Large-Conductance Calcium-Activated Potassium Channel beta Subunits
Physiology
Bicarbonate
Sodium
Potassium
chemistry.chemical_element
Potassium Chloride
Excretion
Mice
chemistry.chemical_compound
Internal medicine
medicine
Animals
Intercalated Cell
Epithelial Sodium Channels
Kidney Tubules, Distal
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
Acidosis
Mice, Knockout
Chemistry
Potassium, Dietary
Nephrons
Articles
medicine.disease
Mice, Inbred C57BL
Bicarbonates
Endocrinology
Models, Animal
medicine.symptom
Subjects
Details
- ISSN :
- 15221466 and 1931857X
- Volume :
- 303
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Renal Physiology
- Accession number :
- edsair.doi.dedup.....2d86555c32142896efa867bc99eebd97