Dietary Cl−restriction upregulates pendrin expression within the apical plasma membrane of type B intercalated cells

Abstract

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 cytoplasmic pendrin immunolabel 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 excreted more Cl−and had a higher arterial pH than pair-fed wild-type mice. In conclusion, 1) following dietary Cl−restriction, apical plasma membrane pendrin immunolabel increases in type B intercalated cells, but not in non-A, non-B intercalated cells; and 2) pendrin participates in the regulation of renal Cl−excretion and arterial pH during dietary Cl−restriction.