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

Net HCO3- transport in the rabbit kidney cortical collecting duct (CCD) is mediated by simultaneous H+ secretion and HCO3- secretion, most likely occurring in alpha- and p-intercalated cells (lCs), 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 similar to 2 pmol/min per mm before acid incubation, whereas after incubation these agents inhibited net HCO; absorption by similar to 5 pmol/min per mm. Inhibition of beta-IC function (luminal Cl- removal) inhibited HCO3- secretion by similar to 9 pmol-min per mm before incubation, whereas after incubation HCO3- absorption was stimulated by only similar to 3 pmol/min per mm. After acid incubation, luminal SCH28080 inhibited HCO3- absorption by only 5-15% vs the similar to 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 bt downregulating HCO3- secretion in beta-ICs via decreased apical Cl-/base exchange activity and upregulating HCO3- absorption in alpha-ICs via increased apical H+-ATPase and baso-lateral 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.