Aquaporin-1 acts as an O channel. The permeability of human and mouse red cell membranes for oxygen.

It has been demonstrated that aquaporin-1 (AQP1), one of the most abundant red cell membrane proteins, constitutes a functionally important channel for CO in red cell membranes. We ask here, whether AQP1 and other gas channel proteins play a role also in red cell oxygen transport. We use a stopped-flow technique to: ) compare the oxygen permeability, [Formula: see text], of AQP1-deficient (Colton Null) with that of normal human red cell membranes, ) compare the [Formula: see text] of with that of normal mouse red cells, ) study the effect of the gas channel inhibitor 4,4'-diisothiocyanato-2,2'-stilbenedisulfonate (DIDS) on [Formula: see text] of human and mouse red cells, and ) investigate all three effects at various temperatures between 7 and 37°C, because O transfer across channels and across membrane lipids may depend differently on temperature. We find that at 7°C/10°C lack of AQP1 in the red cell membrane causes significant reductions of [Formula: see text], by 20% in human and by 37% in mouse red cells. DIDS causes reductions in [Formula: see text] by 34% in human and by 88% in mouse red cells. In addition, the AQP1 inhibitor 5-(phenoxymethyl)furan-2-carbaldehyde (5-PMFC) decreases human red cell [Formula: see text] by ∼40%. All these effects are highly visible at 7°C/10°C, but minor or absent at 25 and 37°C, suggesting that O passage through the channel(s) increases less with temperature than O permeation through membrane lipids. Lack of AQP1 and exposure to DIDS or 5-PMFC indicate that AQP1-possibly along with other gas channels-at <25°C acts as an efficient channel for O. Aquaporin-1 is a membrane protein that conducts CO at 37°C very efficiently. Here, we show that aquaporin-1 also conducts O, but mainly at lower temperatures of around 10°C. Although O transfer across the red cell membrane is accelerated by aquaporin-1 significantly at 10°C, a temperature occurring in poikilotherms, aquaporin-1 apparently does not contribute to O passage at 37°C as it occurs in homoiotherms.