On the mechanism of bicarbonate exit from renal proximal tubular cells

On the mechanism of bicarbonate exit from renal proximal tubular cells. We compare here the results of electrophysiological measurements on proximal tubular cells performed on rat kidney in vivo and on isolated rabbit and rat tubules in vitro . Based on different effects of carbonic anhydrase inhibitors in the in vivo and in vitro preparation, we conclude that NaHCO 3 cotransport across the basolateral cell membrane functions as Na + -CO 3 2 − -HCO 3 − cotransport in vivo , but as Na + -HCO 3 − -HCO 3 − cotransport in the classical in vitro preparation. The former, but not the latter, transport mode is characterized by generation of local disequilibrium pH / CO 3 2 − concentrations that oppose fluxes if membrane-bound carbonic anhydrase is inhibited. In support of this conclusion, we find that overall transport functions with a HCO 3 − to Na + stoichiometry of 3:1 in vivo (since each transported CO 3 2 − eventually generates 2 HCO 3 − ions), but 2:1 in vitro . This has been deduced from various measurements, among them super-Nernstian and reverse Nernstian, potential responses to changing ion concentrations which are characteristic of obligatorily coupled cation-anion cotransporters, but are not known in classical electrochemistry. The different transport modes in vivo and in vitro suggest that isolated proximal tubules have functional deficits compared to proximal tubules in vivo .