Red cell membrane CO2 permeability in normal human blood and in blood deficient in various blood groups, and effect of DIDS

The red cell membrane has an exceptionally high permeability for CO2, PCO2 ≈ 0.15 cm/s, which is two to three orders of magnitude greater than that of some epithelial membranes and similarly greater than the permeability of the red cell membrane for HCO3–. As shown previously, this high PCO2 can be drastically inhibited by 10 μM 4,4′-diisothiocyanato-2,2′-stilbenedisulfonate (DIDS), indicating that membrane proteins may be involved in this high gas permeability. Here, we have studied the possible contribution of several blood group proteins to CO2 permeation across the red cell membrane by comparing PCO2 of red cells deficient in specific blood group proteins with that of normal red cells. While PCO2 of normal red cells is ~0.15 cm/s and that of Fynull and Jknull red cells is similar, PCO2's of Colton null (deficient in aquaporin-1) and Rhnull cells (deficient in Rh/RhAG) are both reduced to about 0.07 cm/s, i.e. to about one half. In addition, the inhibitory effect of DIDS is about half as great in Rhnull and in Colton null red cells as it is in normal red cells. We conclude that aquaporin-1 and Rh/RhAG proteins contribute substantially to the high permeability of the human red cell membrane for CO2. Together these proteins are responsible for 50% or more of the CO2 permeability of red cell membranes. The CO2 pathways of both proteins can be partly inhibited by DIDS, which is why this compound very effectively reduces membrane CO2 permeability.