The physiological response of the carotid body is critically dependent upon oxygen-sensing by potassium channels expressed in glomus cells. One such channel is the large conductance, voltage- and calcium-dependent potassium channel, BKCa. Although it is well known that a decrease in oxygen evokes glomus cell depolarization, voltage-gated calcium entry, and transmitter release, the molecular identity of the upstream oxygen sensor has been the subject of some controversy for decades. Recently, we have demonstrated that hemeoxygenase-2 associates tightly with recombinant BKCa and that activity of this enzyme confers oxygen sensitivity to the BKCa channel complex. Similar observations were also made in native channels recorded from carotid body glomus cells, suggesting that hemoxygenase-2 functions as an oxygen sensor of native and recombinant BKCa channels. (c) 2005 Elsevier Inc. All rights reserved.