Hypoxic inhibition of background K + channels is crucial to O 2 sensing by chemoreceptor tissues, but direct demonstration of O 2 sensitivity by any member of this K + channel family is lacking. HEK293 cells were transfected with a pcDNA3.1-hTASK1 construct; expression of hTASK1 was verified using RT-PCR and immunocytochemistry. Whole-cell K + currents of cells stably expressing hTASK-1 were, as anticipated, extremely sensitive to extracellular pH, within the physiological range (IC 50 ≈ 7.0). All cells expressing this signature pH sensitivity were acutely modulated by pO 2 ; reduction of pO 2 from 150 to <40 mmHg (at pH 7.4) caused rapid and reversible suppression of pH-sensitive K + currents. Furthermore, these two regulatory signals clearly acted at the same channel, since the magnitude of the O 2 -sensitive current was dependent on the extracellular pH. These data represent the first direct verification that hTASK1 is O 2 -sensitive and reinforce the idea that this K + channel is key to O 2 sensing in chemoreceptors.