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Am J Physiol Renal Physiol 284: F103-F112, 2003. First published August 13, 2002; doi:10.1152/ajprenal.00205.2002
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Vol. 284, Issue 1, F103-F112, January 2003

Regulation of the apical Clminus /HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> exchanger pendrin in rat cortical collecting duct in metabolic acidosis

Snezana Petrovic1,2, Zhaohui Wang1, Liyun Ma1, and Manoocher Soleimani1,2

1 Department of Medicine, University of Cincinnati, and 2 Veterans Affairs Medical Center at Cincinnati, Cincinnati, Ohio 45267-0485

Pendrin is an apical Cl-/OH-/HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> exchanger in beta -intercalated cells (beta -ICs) of rat and mouse cortical collecting duct (CCD). However, little is known about its regulation in acid-base disorders. Here, we examined the regulation of pendrin in metabolic acidosis, a condition known to decrease HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> secretion in CCD. Rats were subjected to NH4Cl loading for 4 days, which resulted in metabolic acidosis. Apical Cl-/HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> exchanger activity in beta -ICs was determined as amplitude and rate of intracellular pH change when Cl was removed in isolated, microperfused CCDs. Intracellular pH was measured by single-cell digital ratiometric imaging using fluorescent pH-sensitive dye 2',7'-bis-(3-carboxypropyl)-5-(and-6)-carboxyfluorescein-AM. Pendrin mRNA expression in kidney cortex was examined by Northern blot hybridizations. Expression of pendrin protein was assessed by indirect immunofluorescence. Microperfused CCDs isolated from acidotic rats demonstrated ~60% reduction in apical Cl-/HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> exchanger activity in beta -ICs (P < 0.001 vs. control). Northern blot hybridizations indicated that the mRNA expression of pendrin in kidney cortex decreased by 68% in acidotic animals (P < 0.02 vs. control). Immunofluorescence labeling demonstrated significant reduction in pendrin expression in CCDs of acidotic rats. We conclude that metabolic acidosis decreases the activity of the apical Cl-/HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> exchanger in beta -ICs of the rat CCD by reducing the expression of pendrin. Adaptive downregulation of pendrin in metabolic acidosis indicates the important role of this exchanger in acid-base regulation in the CCD.

kidney; intercalated cells


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