Cellular distribution of oxygen sensor candidates—Oxidases, cytochromes, K⁺‐channels—in the carotid body

Abstract

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.

Peripheral Chemoreceptors: Function and Plasticity of the Carotid Body

“…The mitochondria of type I cells are different in appearance to those found in both type II cells and sinus nerve endings, with those in the type I cells being the largest with the most cristae and a relatively light matrix (485). Whether these morphological differences are significant for the expression of cell-specific, mitochondrial proteins is not yet known, but mitochondrial function appears closely tied with O 2 sensing and it is apparent that pharmacologically mediated changes in mitochondrial respiration can act like hypoxia to increase Ca 2+ influx and elevate [Ca 2+ ] i (77, 109, 918), induce neurosecretion (748), and cause cell depolarization by inhibition of ca .…”

“…This K B channel is highly expressed in the type I cell where its properties support the existence of TASK-1-like (112) and TASK-3-like (911) subunit activities that are likely a consequence of a TASK1/3 heterodimer that contributes the principal component of the K B conductance (438, 441). In addition, TASK-2 and TWIK-related arachidonic acid-stimulated K + channel (TRAAK) have also been localized by immunohistochemisty to the type I cell (928) and TASK-1 immunoreactivity has also been reported in the mouse carotid body (423) and human carotid body (261) as well as on rat type II cells (485), although their function on these latter cells has not been determined. The channel has a characteristic, low conductance of ca .…”

Heterogeneous expression of TASK-3 and TRAAK in rat paraganglionic cells

“…One of the convincing candidates for the oxygen sensor in carotid body chief cells is the two-pore K + channel, or TASK family (Buckler et al 2000;Kummer and Yamamoto 2002;Yamamoto et al 2002). Hartness et al (2001) reported that the neuroepithelial cell line H146 expressed TASK1 and TASK3, and that hypoxic inhibition of the K + current was abrogated by injection of antisense oligodeoxynucleotides for human TASK1/TASK3.…”

Hypoxie-induzierte Freisetzung reaktiver Sauerstoffspezies (ROS) in isoliert perfundierten und ventilierten Mauslungen

“…Andere Arbeitsgruppen konnten zudem zeigen, dass die HPV vom Sauerstoffpartialdruck (PO 2 ) im Blut unabhängig ist und allein durch den PO 2 im Alveolarraum gesteuert wird. Weitere hypothetisch in Frage kommende Sauerstoffsensoren sind Zytochrom P450, das unter Hypoxie oxidiert werden soll (Acker et al, 2006;Fleming et al, 2001;Kummer and Yamamoto, 2002;Porwol et al, 2001;Sylvester and McGowan, 1978), NO-Synthasen, die durch Hypoxie inhibiert werden sollen Dumitrascu et al, 2006;Landmesser et al, 2003;Weissmann et al, 2003b), Mitochondrien (Archer et al, 2006b;Archer et al, 2004;Michelakis et al, 2002;Michelakis et al, 2004;Waypa et al, 2001;Zwicker et al, 1998) phagozytäre und nicht-phagozytäre NADP(H)-Oxidasen (Babior, 2004;Brennan et al, 2003;Ellmark et al, 2005;Liu et al, 2006;Weissmann et al, 2006c).…”

“…Durch die ROS-Produktion soll das intrazelluläre RedoxPotential verändert und auf diese Weise das Signal weitergeleitet werden, das letztendlich durch Konformationsänderung der K V zur Kontraktion der glatten Muskelzellen unter Hypoxie führt (Gupte and Wolin, 2006;Kummer and Yamamoto, 2002;Lopez-Barneo et al, 2004;Waypa et al, 2001;Weir et al, 2002;Weissmann et al, 2003a;Wolin et al, 2005). Offen hingegen ist die Frage, welche Strukturen zur ROS-Produktion unter Hypoxie beitragen und ob es zu einer vermehrten oder verminderten Freisetzung der Radikale kommt (Aaronson, 2006;Aaronson et al, 2006;Rojas et al, 2006;Sham, 2002;Sylvester, 2001;Weissmann et al, 2006b).…”