Cellular mechanisms of oxygen sensing at the carotid body: heme proteins and ion channels

The purpose of this article is to highlight some recent concepts on oxygen sensing mechanisms at the carotid body chemoreceptors. Most available evide nce suggests that glomus (type I) cells are the initial site of transductio n and they release transmitters in response to hypoxia. which in turn depol arize the nearby afferent nerve ending, leading to an increase in sensory d ischarge. Two main hypotheses have been advanced to explain the initiation of the transduction process that triggers transmitter release. One hypothes is assumes that a biochemical event associated with a heme protein triggers the transduction cascade. Supporting this idea it has been shown that hypo xia affects mitochondrial cytochromes. In addition, there is a body of evid ence implicating non-mitochondrial enzymes such as NADPH oxidases, NO synth ases and heme oxygenases located in glomus cells. These proteins could cont ribute to transduction via generation of reactive oxygen species, nitric ox ide and/or carbon monoxide. The other hypothesis suggests that a K+ channel protein is the oxygen sensor and inhibition of this channel and the ensuin g depolarization is the initial event in transduction. Several oxygen sensi tive K+ channels have been identified. However, their roles in initiation o f the transduction cascade and/or cell excitability are unclear. In additio n, recent studies indicate that molecular oxygen and a variety of neurotran smitters may also modulate Ca2+ channels. Most importantly, it is possible that the carotid body response to oxygen requires multiple sensors, and the y work together to shape the overall sensory response of the carotid body o ver a wide range of arterial oxygen tensions. (C) 2000 Elsevier Science B.V . All rights reserved.