We have recently reported that the model airway chemoreceptors, H146 cells, exhibit a significant component of their oxygen-sensing transduction pathway which cannot be explained by activity of NADPH oxidase. Using patch-clamp, we have studied the transduction system linking reduced O-2 to K+ channel inhibition and report that, in complete contrast to recent suggestions in pulmonary vasculature, O-2 sensing by the model airway chemoreceptors, H146 cells, does not require functional mitochondria. These data show, for the first time, that mitochondrial production of reactive O-2 species is not the unifying mechanism in O-2 sensing. (C) 2002 Elsevier Science (USA).