Combined antisense and pharmacological approaches implicate hTASK as an airway O-2 sensing K+ channel

Neuroepithelial bodies act as airway oxygen sensors. The lung carcinoma lin e H146 is an established model for neuroepithelial body cells. Although O-2 sensing in both cells is via NADPH oxidase H2O2/free radical production an d acute hypoxia promotes K+ channel closure and cell depolarization, the id entity of the K+ channel is still controversial. However, recent data point toward the involvement of a member of the tandem P domain family of K+ cha nnels. Reverse transcription-polymerase chain reaction screening indicates that all known channels other than hTWIK1 and hTRAAK are expressed in H146 cells. Our detailed pharmacological characterization of the O-2-sensitive K + current described herein is compatible with the involvement of hTASK1 or hTASK3 (pH dependence, tetraethylammonium and dithiothreitol insensitivity, blockade by arachidonic acid, and halothane activation). Furthermore, we h ave used antisense oligodeoxynucleotides directed against hTASK1 and hTASK3 to suppress almost completely the hTASK1 protein and show that these cells no longer respond to acute hypoxia; this behavior was not mirrored in lipo some-only or missense-treated cells. Finally, we have used Zn2+ treatment a s a maneuver able to discriminate between these two homologues of hTASK and show that the most likely candidate channel for O-2 sensing in these cells is hTASK3.