We have previously shown that DIDS is an efficient inhibitor of the permeability of the red cell (RBC) for CO2 (PCO2 ). As DIDS is also a potent inhibitor of the anion exchanger AE1, it appeared possible that CO2 entry into the RBC is based on HCO3- transfer via AE1, equivalent transfer of H+ via a proton (or OH-) pathway, and subsequent carbonic anhydrase (CA)-catalysed recombination of both ions to yield CO2 right after membrane passage. To test this hypothetical mechanism we have studied i)the effects of several other inhibitors of AE1 on PCO2 , and ii) the effect of lack of CAII, which is thought to be normally entirely associated with AE1 on the internal side of the membrane. We found that two other inihibitors of AE1, DiBAC and phloretin, while effectively reducing HCO3- transport, in contrast to DIDS do not affect PCO2 . Similarly, CAII-deficient human red cells showed no major reduction in PCO2 compared to normal RBCs. We conclude that the proposed mechanism of CO2 transfer is not supported by experimental data and that very likely CO2 traverses the membrane in gaseous form.

Supported by DFG Gr 489/19.