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/HCO
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
-intercalated cells (-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/HCO-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-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-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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