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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 295/6/C1658    most recent 00419.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Hafner, P. Articles by Wagner, C. A. Search for Related Content PubMed PubMed Citation Articles by Hafner, P. Articles by Wagner, C. A.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Pendrin in the mouse kidney is primarily regulated by Cl^– excretion but also by systemic metabolic acidosis

¹Institute of Physiology and Center for Human Integrative Physiology, University of Zurich, Zurich, Switzerland; and ²School of Medicine, Second University of Naples, Naples, Italy

Submitted 14 August 2008 ; accepted in final form 23 October 2008

The Cl^–/anion exchanger pendrin (SLC26A4) is expressed on the apical side of renal non-type A intercalated cells. The abundance of pendrin is reduced during metabolic acidosis induced by oral NH₄Cl loading. More recently, it has been shown that pendrin expression is increased during conditions associated with decreased urinary Cl^– excretion and decreased upon Cl^– loading. Hence, it is unclear if pendrin regulation during NH₄Cl-induced acidosis is primarily due the Cl^– load or acidosis. Therefore, we treated mice to increase urinary acidification, induce metabolic acidosis, or provide an oral Cl^– load and examined the systemic acid-base status, urinary acidification, urinary Cl^– excretion, and pendrin abundance in the kidney. NaCl or NH₄Cl increased urinary Cl^– excretion, whereas (NH₄)₂SO₄, Na₂SO₄, and acetazolamide treatments decreased urinary Cl^– excretion. NH₄Cl, (NH₄)₂SO₄, and acetazolamide caused metabolic acidosis and stimulated urinary net acid excretion. Pendrin expression was reduced under NaCl, NH₄Cl, and (NH₄)₂SO₄ loading and increased with the other treatments. (NH₄)₂SO₄ and acetazolamide treatments reduced the relative number of pendrin-expressing cells in the collecting duct. In a second series, animals were kept for 1 and 2 wk on a low-protein (20%) diet or a high-protein (50%) diet. The high-protein diet slightly increased urinary Cl^– excretion and strongly stimulated net acid excretion but did not alter pendrin expression. Thus, pendrin expression is primarily correlated with urinary Cl^– excretion but not blood Cl^–. However, metabolic acidosis caused by acetazolamide or (NH₄)₂SO₄ loading prevented the increase or even reduced pendrin expression despite low urinary Cl^– excretion, suggesting an independent regulation by acid-base status.

transporter; collecting duct