RhAG protein of the Rhesus complex is a CO2 channel in the human red cell membrane

We have determined CO2 permeabilities, P-CO2, of red cells of normal human blood and of blood deficient in various blood group proteins by a previously described mass spectrometric technique. While PCO2 of normal red cells is similar to 0.15 cm/s, we find in red blood cells (RBCs) lacking the Rh protein complex (Rh-null) a significantly reduced P-CO2 of 0.07 cm/s +/- 0.02 cm/s (P< 0.02). This value is similar to the value we have reported previously for RBCs lacking aquaporin-1 protein (AQP-1(null)), suggesting that each of the Rh and AQP-1 proteins is responsible for similar to 1/2 of the normal CO2 permeability of the RBC membrane. Four other blood group deficiencies tested lack diverse membrane proteins but exhibit normal CO2 permeability. The CO2 pathway constituted by Rh proteins was inhibitable at pH(e) = 7.4 by NH4Cl with an I-50 of similar to 10 mM corresponding to an I50 for NH3 of similar to 0.3 mM. The pathway independent of Rh proteins, presumably that constituted by AQP-1, was not inhibitable by NH4Cl/NH3. However, both pathways were strongly inhibited by DIDS, which accounts for the marked inhibitory effect of DIDS on normal PCO2, while in contrast another AE1 inhibitor, DiBAC, does not inhibit PCO2, although it markedly reduces PHCO3-. We conclude that Rh protein, presumably the Rh-associated glycoprotein RhAG, possesses a gas channel that allows passage of CO2 in addition to NH3.-Endeward, V., Cartron, J.-P., Ripoche, P., and Gros, G. RhAG protein of the Rhesus complex is a CO2 channel in the human red cell membrane.