Acetazolamide inhibition of basolateral base exit in rabbit renal proximal tubule S2 segment.

The influence of the carbonic anhydrase inhibitor acetazolamide (ACZ) was investigated on HCO3- transport mechanisms in the basolateral cell membrane of rabbit renal proximal tubule. Experiments were performed on isolated S2 segments using double-barrelled microelectrodes to measure cell membrane potential (Vb) and cell pH (pH(i)) during step changes in bath perfusate ion concentrations. Peritubular application of ACZ (1 mmol/l) reduced the initial Vb response to 10:1 reduction of bath HCO3- concentration only slightly, from +53.8 +/- 4.2 mV to +49.1 +/- 0.3 mV (n = 5), but caused an intermittent overshooting repolarization in the secondary Vb response. In conjunction with these effects it left the initial pH(i)) response virtually unchanged but induced a secondary slow acidification. These observation indicate that--under the present experimental conditions--ACZ does not block the Na(+)-HCO3- cotransporter but acts via inhibition of cytosolic carbonic anhydrase. This was confirmed by studying the effect of elevated intracellular HCO3- concentrations under reduced flux conditions and by comparing the concentration dependence of the Vb response with the inhibition kinetics of cytosolic carbonic anhydrase. In contrast, peritubular ACZ inhibited Na(+)-independent Cl-/HCO3- exchange in the basolateral cell membrane of S2 segments directly in a similar way to that described in the preceding publication for S3 segments.