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Intercalated cell H+/OH- transporter expression is reduced in Slc26a4 null mice
Young-Hee Kim1, Jill W Verlander, Sharon W Matthews
1Department of Medicine, Emory University, Atlanta, Georgia, USA.
American Journal of Physiology. Renal Physiology
|September 8, 2005
Summary
Genetic disruption of Slc26a4 (pendrin) in mice does not alter acid-base balance but reduces urinary buffering and kidney transporter expression. This compensates for altered acid-base regulation in Slc26a4 null mice.
Area of Science:
- Nephrology
- Physiology
- Molecular Biology
Background:
- Slc26a4 (pendrin) is a Cl(-)/HCO(3)(-) exchanger involved in OH(-) secretion.
- Genetic disruption of Slc26a4 can lead to alkalosis in some models.
- However, Slc26a4 null humans and mice maintain normal acid-base balance basally.
Purpose of the Study:
- To investigate if Slc26a4 null mice have altered net acid excretion under basal conditions.
- To determine if changes in intercalated cell subtypes or transporter expression minimize pH increases in the absence of pendrin.
- To understand the compensatory mechanisms for pendrin deficiency in acid-base homeostasis.
Main Methods:
- Balance studies to measure net acid excretion (ammonium, titratable acid, citrate).
- Immunolocalization and immunoblotting to assess intercalated cell subtype abundance and H(+)/OH(-) transporter expression (H+-ATPase, NBC3, RhBG, RhCG).
- Analysis of urinary pH and Pco(2) in Slc26a4 null and wild-type mice.
Main Results:
- Net acid excretion components were similar between Slc26a4 null and wild-type mice.
- Slc26a4 null mice exhibited lower urinary pH and Pco(2) due to reduced HCO(3)(-) buffering.
- Reduced abundance of non-A intercalated cells and decreased expression of H+-ATPase, NBC3, and RhBG were observed in Slc26a4 null kidneys.
Conclusions:
- Slc26a4 null mice show compensatory mechanisms to maintain acid-base balance.
- Reduced urinary buffering and altered expression of kidney H(+)/OH(-) transporters attenuate potential pH increases.
- These adaptations highlight the kidney's role in maintaining systemic pH homeostasis despite pendrin deficiency.