K:Cl cotransport in red cells of transgenic mice expressing high levels of human hemoglobin Ss

K:Cl cotransport is involved in generating dense red blood cells (RBCs) in homozygotes for HbS (SS). We report on the properties of this transport system in RBCs from control and transgenic mice expressing high levels of human α(H) and β(s) chains. Unlike human SS RBCs, mouse RBCs incubated in isotonic media exhibited a Cl^--dependent K⁺ efflux and therefore have e different set-point for activation. This basal efflux was slightly stimulated by cell swelling to values five times smaller than that in human SS cells; in addition, the delay time for activation was shorter in transgenic than in control mice, but fourfold longer than that of human SS ceils. These properties cast doubt on the physiological impact of the mouse K:Cl cotransporter on RBC volume regulation in the mouse and suggest that there are intrinsic differences between the human K:Cl cotransporter and the putative transporter in mice.