Laboratory Investigation

Kidney International (1997) 51, 125–137; doi:10.1038/ki.1997.16

Regulation of AE1 anion exchanger and H+-ATPase in rat cortex by acute metabolic acidosis and alkalosis

Ivan Sabolic acute, Dennis Brown, Stephen L Gluck and Seth L Alper

Institute for Medical Research and Occupational Health, Zagreb, Croatia, Renal Unit, Massachusetts General Hospital, Molecular Medicine and Renal Units, Beth Israel Hospital, Departments of Pathology, Cell Biology, and Medicine, Harvard Medical School, Boston, Massachusetts; and Departments of Cell Biology and Medicine, Washington University School of Medicine, St. Louis, Missouri, USA

Correspondence: Seth L Alper MD, Molecular Medicine Unit, Beth Israel Hospital, 330 Brookline Ave., Boston, Massachusetts 02215, USA. E-mail: salper@bih.harvard.edu

Received 22 April 1996; Revised 31 July 1996; Accepted 5 August 1996.

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Abstract

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.

Abbreviations:

IC, intercalated cells; CCD, cortical collecting duct; CNT, connecting segment; PLP, paraformaldehyde/lysine/periodate; PC, principal cells; PBS, phosphate-buffered saline

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