The mammalian carotid body in the neck is a chemoreceptor that senses O2 levels in the circulatory system and adjusts the respiratory rate accordingly. When O2 becomes scarce, large-conductance calcium-sensitive potassium (BK) channels become inhibited, which causes cell depolarization and a cascade of responses that ultimately increases ventilation. Williams et al. (see the Perspective by Hoshi and Lahiri) now find that hemoxygenase-2 (HO-2) acts as an O2 sensor to control BK channel activity. At normal O2 concentrations, HO-2 uses O2 as a substrate to generate carbon monoxide (CO), a critical channel activator. During hypoxia, when O2 becomes scarce, HO-2 activity and CO generation fall, which inhibits BK channels and results in carotid body excitation.
S. E. J. Williams, P. Wootton, H. S. Mason, J. Bould, D. E. Iles, D. Riccardi, Chris Peers, P. J. Kemp, Hemoxygenase-2 is an oxygen sensor for a calcium-sensitive potassium channel. Science 306, 2093-2097 (2004). [Abstract] [Full Text]