title: Adaptation of rabbit cortical collecting duct HCO3- transport to metabolic acidosis in vitro.
abstract: Net HCO3- transport in the rabbit kidney cortical collecting duct (CCD) is mediated by simultaneous H+ secretion and HCO3- secretion, most likely occurring in a alpha- and beta-intercalated cells (ICs), respectively. The polarity of net HCO3- transport is shifted from secretion to absorption after metabolic acidosis or acid incubation of the CCD. We investigated this adaptation by measuring net HCO3- flux before and after incubating CCDs 1 h at pH 6.8 followed by 2 h at pH 7.4. Acid incubation always reversed HCO3- flux from net secretion to absorption, whereas incubation for 3 h at pH 7.4 did not. Inhibition of alpha-IC function (bath CL- removal or DIDS, luminal bafilomycin) stimulated net HCO3- secretion by approximately 2 pmol/min per mm before acid incubation, whereas after incubation these agents inhibited net HCO3- absorption by approximately 5 pmol/min per mm. Inhibition of beta-IC function (luminal Cl- removal) inhibited HCO3- secretion by approximately 9 pmol/min per mm before incubation, whereas after incubation HCO3- absorption by only 3 pmol/min per mm. After acid incubation, luminal SCH28080 inhibited HCO3- absorption by only 5-15% vs the circa 90% inhibitory effect of bafilomycin. In outer CCDs, which contain fewer alpha-ICs than midcortical segments, the reversal in polarity of HCO3- flux was blunted after acid incubation. We conclude that the CCD adapts to low pH in vitro by downregulation HCO3- secretion in beta-ICs via decreased apical CL-/base exchang activity and upregulating HCO3- absorption in alpha-ICs via increased apical H+ -ATPase and basolateral CL-/base exchange activities. Whether or not there is a reversal of IC polarity or recruitment of gamma-ICs in this adaptation remains to be established.
authors.affiliation: Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
authors.forename: S
authors.initials: S
authors.lastname: Tsuruoka
authors.forename: G J
authors.initials: GJ
authors.lastname: Schwartz
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D046508:Culture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007672:Kidney Cortex / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism*; D018942:Macrolides; D008564:Membrane Potentials / Q000187:drug effects; D054328:Proton Pump Inhibitors; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D011817:Rabbits
chemical_list: D000900:Anti-Bacterial Agents; D001639:Bicarbonates; D002712:Chlorides; D004791:Enzyme Inhibitors; D007093:Imidazoles; D018942:Macrolides; D054328:Proton Pump Inhibitors; C035235:Sch 28080; C040929:bafilomycin A1; D006180:Proton-Translocating ATPases; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid