ON THE MECHANISM OF BICARBONATE EXIT FROM RENAL PROXIMAL TUBULAR CELLS

We compare here the results of electrophysiological measurements on pr oximal tubular cells performed on rat kidney in vivo and on isolated r abbit and rat tubules in vitro. Based on different effects of carbonic anhydrase inhibitors in the in vivo and in vitro preparation, we conc lude that NaHCO3 cotransport across the basolateral cell membrane func tions as Na+-CO32--HCO3- cotransport in vivo, but as Na+-HCO3--HCO3- c otransport in the classical in vitro preparation. The former, but not the latter, transport mode is characterized by generation of local dis equilibrium pH/CO32- concentrations that oppose fluxes if membrane-bou nd carbonic anhydrase is inhibited. In support of this conclusion, we find that overall transport functions with a HCO3- to Na+ stoichiometr y of 3:1 in vivo (since each transported CO32- eventually generates 2 HCO3- ions), but 2:1 in vitro. This has been deduced from various meas urements, among them super-Nernstian and reverse Nernstian, potential responses to changing ion concentrations which are characteristic of o bligatorily 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 defici ts compared to proximal tubules in vivo.