Adaptation of rabbit cortical collecting duct HCO3- transport to metabolic acidosis in vitro

J Clin Invest. 1996 Feb 15;97(4):1076-84. doi: 10.1172/JCI118500.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
  • Acidosis / metabolism*
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bicarbonates / metabolism*
  • Biological Transport / drug effects
  • Chlorides / metabolism
  • Culture Techniques
  • Enzyme Inhibitors / pharmacology
  • Female
  • Imidazoles / pharmacology
  • Kidney Cortex / metabolism
  • Kidney Tubules, Collecting / cytology
  • Kidney Tubules, Collecting / metabolism*
  • Macrolides*
  • Membrane Potentials / drug effects
  • Proton Pump Inhibitors
  • Proton-Translocating ATPases / antagonists & inhibitors
  • Rabbits

Substances

  • Anti-Bacterial Agents
  • Bicarbonates
  • Chlorides
  • Enzyme Inhibitors
  • Imidazoles
  • Macrolides
  • Proton Pump Inhibitors
  • Sch 28080
  • bafilomycin A1
  • Proton-Translocating ATPases
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid