In excitable cells, hypoxia inhibits K channels, causes membrane depolarization and initiates complex adaptive mechanisms. It is unclear whether K channels of alveolar epithelial cells reveal a similar response to hypoxia. A549 cells were exposed to hypoxia during whole cell patch clamp measurements. Hypoxia reversibly inhibited a voltage-dependent outward current consistent with a potassium current since tetraethylamonium (TEA; 10 mM) abolished this effect, but iberiotoxin (0.1µM) does not. In normoxia TEA and iberiotoxin inhibited whole cell current (- 35%) while the K-channel inhibitors glibenclamide (1µM), barium (1mM), chromanol B293 (10µM) and 4-aminopyridine (1mM) were ineffective. ⁸⁶Rb uptake was measured to see, whether K-channel modulation also affected transport activity. TEA, iberiotoxin and 4h hypoxia (1.5 % O₂) inhibited total ⁸⁶Rb uptake by 40%, 20% and 35%, respectively. Increased extracellular K also inhibited ⁸⁶Rb uptake in a dose dependent way. The K channel opener 1-EBIO (1mM) increased ⁸⁶Rb uptake by 120% in normoxic and hypoxic cells by activation of Na/K-pumps (+ 60%) and Na/K/2Cl-cotransport (+ 170%). However, transport inhibition was also seen in presence of 1-EBIO, TEA and iberiotoxin. These results indicate that hypoxia, membrane depolarization and K-channel inhibition decreases whole cell membrane currents and transport activity. It appears therefore that an hypoxia-induced change in membrane conductance and membrane potential might be a link between hypoxia and alveolar ion transport inhibition.