Adaptation of Rabbit Cortical Collecting Duct HCO Transport to Metabolic Acidosis In Vitro

Net HCO transport in the rabbit kidney cortical collecting duct (CCD) is mediated by simultaneous H 1 secretion and HCO secretion, most likely occurring in a and b -intercalated cells (ICs), respectively. The polarity of net HCO transport is shifted from secretion to absorption after metabolic acidosis or acid incubation of the CCD. We investigated this adaptation by measuring net HCO flux before and after incubating CCDs 1 h at pH 6.8 followed by 2 h at pH 7.4. Acid incubation always reversed HCO flux from net secretion to absorption, whereas incubation for 3 h at pH 7.4 did not. Inhibition of a -IC function (bath Cl 2 removal or DIDS, luminal bafilomycin) stimulated net HCO secretion by z 2 pmol / min per mm before acid incubation, whereas after incubation these agents inhibited net HCO absorption by z 5 pmol / min per mm. Inhibition of b -IC function (luminal Cl 2 removal) inhibited HCO secretion by z 9 pmol / min per mm before incubation, whereas after incubation HCO absorption was stimulated by only z 3 pmol / min per mm. After acid incubation, luminal SCH28080 inhibited HCO absorption by only 5–15% vs the z 90% inhibitory effect of bafilomycin. In outer CCDs, which contain fewer a -ICs than midcortical segments, the reversal in polarity of HCO flux was blunted after acid incubation. We conclude that the CCD adapts to low pH in vitro by downregulating HCO secretion in b -ICs via decreased apical Cl 2 / base exchange activity and upregulating HCO absorption in a -ICs via increased apical H 1 -ATPase and basolateral Cl 2 / base exchange activities. Whether or not there is a reversal of IC polarity or recruitment of g -ICs in this adaptation remains to be established. ( J. Clin. Invest. 1996. 97: 1076–1084).