Cellular distribution of oxygen sensor candidates-oxidases, cytochromes, K+-channels--in the carotid body.
The specific tissue of the carotid body is built up of groups of glomus cells, enveloped by glial-type sustentacular cells, and innervated by sensory nerve fibers. These units sense arterial pO(2) and respond to hypoxia by a variety of reactions that include initiation of the arterial chemoreflex, i.e., increasing firing activity in the carotid sinus nerve. Until now, neither the cellular localization of the initial events that lead to stimulation of chemoreceptor afferents nor the molecular mechanism of oxygen sensing in the carotid body have been unequivocally identified. Proposed molecular candidates for the mechanism of oxygen sensing include: 1). components of the mitochondrial respiratory chain, 2). NADPH oxidases generating reactive oxygen species in an oxygen-dependent manner, 3). oxygen-regulated plasmalemmal K(+)-channels, and 4). nonoxidase iron-proteins. Our still limited knowledge on their cellular distribution within the carotid body is reviewed here. It is evident that: 1). the distribution of at least some oxygen sensor candidates is not ubiquitous but cell-type-specific, and 2). each specific parenchymal cell type of the carotid body contains at least one of the proposed oxygen sensor candidates. This applies also for the glial-type sustentacular cells that exhibit immunoreactivity to the two-pore domain K(+)-channel, TASK-1. These observations fit best with the assumption that each cell type within the carotid body is principally responsive to hypoxia. The differential equipping of glomus cells, nerve endings, and sustentacular cells with sensor proteins might serve to determine different thresholds of sensitivity and/or to connect the process of oxygen sensing to different signaling pathways. It also favors the assumption that several mechanisms of oxygen sensing may act simultaneously. The cellular identification of the cell type initiating the chemoreceptor reflex, however, has to await the molecular identification of the particular oxygen sensor molecule that initiates increased carotid sinus nerve activity.
Kummer
Wolfgang
W
Institute for Anatomy and Cell Biology, Justus-Liebig-University, 35385 Giessen, Germany. wolfgang.kummer@anatomie.med.uni-giessen.de
Yamamoto
Yoshio
Y
D000818:Animals; D002344:Carotid Body / Q000166:cytology* / Q000378:metabolism; D002628:Chemoreceptor Cells / Q000166:cytology / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism*; D006801:Humans; D016253:Microscopy, Immunoelectron; D019255:NADPH Oxidases / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain; D051381:Rats
D003580:Cytochromes; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; D019255:NADPH Oxidases; D010100:Oxygen