Regulation of AE1 anion exchanger and H⁺-ATPase in rat cortex by acute metabolic acidosis and alkalosis. The cortical collecting duct (CCD) mediates net secretion or reabsorption of protons according to systemic acid/base status. Using indirect immunofluorescence, we examined the localization and abundance of the vacuolar H⁺-ATPase and the AE1 anion exchanger in intercalated cells (IC) of rat kidney connecting segment (CNT) and CCD during acute (6 hr) metabolic (NH₄Cl) acidosis and respiratory (NaHCO₃) alkalosis. AE1 immunostaining intensity quantified by confocal microscopy was elevated in metabolic acidosis and substantially reduced in metabolic alkalosis. AE1 immunostaining was restricted to Type A IC in all conditions, and the fraction of AE1⁺ IC was unchanged in CNT and CCD. Metabolic acidosis was accompanied by redistribution of H⁺-ATPase immunostaining towards the apical surface of IC, and metabolic alkalosis was accompanied by H⁺-ATPase redistribution towards the basal surface of IC. Therefore, acute metabolic acidosis produced changes consistent with increased activity of Type A IC and decreased activity of Type B IC, whereas acute metabolic alkalosis produced changes corresponding to increased activity of Type B IC and decreased activity of Type A IC. These data demonstrate that acute systemic acidosis and alkalosis modulate the cellular distribution of two key transporters involved in proton secretion in the distal nephron.