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1 Medicine, Emory University, Atlanta, Georgia, United States; Medicine, University of Florida, Gainesville, Florida, United States; Hypertension and Vascular Research Division, Henry Ford Hospital and Wayne State School of Medicine, Detroit, Michigan, United States; Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland, United States; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom; Medicine, University of Texas, Health Sciences Center, Houston, Houston, Texas, United States
2 Medicine, Emory University, Atlanta, Georgia, United States
* To whom correspondence should be addressed. E-mail: smwall{at}emory.edu.
Pendrin, encoded by Slc26a4, is a Cl-/HCO3- exchanger expressed in the apical region of type B and non-A, non-B intercalated cells, which regulates renal NaCl excretion. Dietary Cl- restriction upregulates total pendrin protein expression. Whether the subcellular expression of pendrin and whether the apparent vascular volume contraction observed in Slc26a4 null mice are Cl--dependent, but Na+-independent, is unknown. Thus, the subcellular distribution of pendrin and its role in acid-base and fluid balance were explored using immunogold cytochemistry and balance studies of mice ingesting a NaCl-replete or a Na+-replete, Cl- restricted diet, achieved through substitution of NaCl with NaHCO3. Boundary length and apical plasma membrane pendrin label density each increased by ~60-70% in type B intercalated cells, but not in non-A, non-B cells, whereas pendrin immunolabel density increased ~60% in non-A, non-B intercalated cells, but not in type B cells. Following either NaCl restriction or Cl- restriction alone, Slc26a4 null mice excrete more Cl- and developed a higher arterial pH than pair-fed wild type mice. Conclusions: 1. Following dietary Cl- restriction, apical plasma membrane pendrin immunolabel increases in type B intercalated cells. 2. Pendrin is critical in the regulation of renal Cl- excretion and arterial pH during dietary Cl- restriction.
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