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 evidence suggests that glomus (type I) cells are the initial site of transduction and they release transmitters in response to hypoxia, which in turn depolarize the nearby afferent nerve ending, leading to an increase in sensory discharge. Two main hypotheses have been advanced to explain the initiation of the transduction process that triggers transmitter release. One hypothesis assumes that a biochemical event associated with a heme protein triggers the transduction cascade. Supporting this idea it has been shown that hypoxia affects mitochondrial cytochromes. In addition, there is a body of evidence implicating non-mitochondrial enzymes such as NADPH oxidases, NO synthases and heme oxygenases located in glomus cells. These proteins could contribute to transduction via generation of reactive oxygen species, nitric oxide and/or carbon monoxide. The other hypothesis suggests that a K(+) channel protein is the oxygen sensor and inhibition of this channel and the ensuing depolarization is the initial event in transduction. Several oxygen sensitive K(+) channels have been identified. However, their roles in initiation of the transduction cascade and/or cell excitability are unclear. In addition, recent studies indicate that molecular oxygen and a variety of neurotransmitters may also modulate Ca(2+) channels. Most importantly, it is possible that the carotid body response to oxygen requires multiple sensors, and they work together to shape the overall sensory response of the carotid body over a wide range of arterial oxygen tensions.
Prabhakar
N R
NR
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4970, USA. nrp@po.cwru.edu
Overholt
J L
JL
D000818:Animals; D002344:Carotid Body / Q000201:enzymology / Q000502:physiology*; D002628:Chemoreceptor Cells / Q000201:enzymology / Q000502:physiology*; D006420:Hemeproteins / Q000502:physiology*; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D010100:Oxygen / Q000097:blood / Q000502:physiology*; D010101:Oxygen Consumption / Q000502:physiology
D006420:Hemeproteins; D007473:Ion Channels; D010100:Oxygen