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Although the carotid body (or glomus caroticum) was a structure familiar to anatomists in the XVIIIth century, it was not until the beginning of the XXth century that its role was revealed. It was then that the German physiologist Heinrich Hering described the respiratory reflex and he began to study the anatomical basis of this reflex focusing on the carotid region, and the carotid sinus in particular...
Research on arterial chemoreceptors, particularly on the carotid body, has been fruitful in the last fifty years, to which this review is addressed. The functional anatomy of the organ appears to be well established. The biophysical bases by which glomus cells transduce chemical changes in the milieu intérieur (hypoxia, hypercapnia, acidosis) into electrical and biochemical changes in glomus cells...
Beginning with the pioneering work of Heymans and collaborators in the 1930’s, investigations into the role of the mammalian carotid body (CB) in the control of ventilation have attracted much attention. Progress for many years was restricted to the whole animal and organ level, resulting in characterization of the stimulus-response characteristics of the CB with its afferent nerve supply during exposure...
Researchers have speculated as to the molecular basis of O2 sensing for decades. In more recent years, since the discovery of ion channels as identified effectors for O2 sensing pathways, research has focussed on possible pathways coupling a reduction in hypoxia to altered ion channel activity. The most extensively studied systems are the K+ channels which are inhibited by hypoxia in chemoreceptor...
In the presence of oxygen (O2), carbon monoxide (CO) is synthesised from heme by endogenous hemeoxygenases, and is a powerful activator of BKCa channels. This transduction pathway has been proposed to contribute to cellular O2 sensing in rat carotid body. In the present study we have explored the role that four cysteine residues (C820, C911, C995 and C1028), located in the vicinity of the...
Hypoxic inhibition of K+ channels in type I cells is believed to be of central importance in carotid body chemotransduction. We have recently suggested that hypoxic channel inhibition is mediated by AMP-activated protein kinase (AMPK). Here, we have further explored the modulation by AMPK of recombinant K+ channels (expressed in HEK293 cells) whose native counterparts are considered O2-sensitive in...
Hydrogen sulfide (H2S) is produced endogenously in many types of mammalian cells. Evidence is now accumulating to suggest that H2S is an endogenous signalling molecule, with a variety of molecular targets, including ion channels. Here, we describe the effects of H2S on the large conductance, calcium-sensitive potassium channel (BKCa). This channel contributes to carotid body glomus cell excitability...
Chemoreceptor cells from rabbit carotid body (CB) exhibit transient outward currents reversibly inhibited by low Po2. Molecular and functional dissection of the components of these outward currents indicates that at least two different channels (Kv4.3 and Kv3.4) contribute to this current. Furthermore, several lines of evidence support the conclusion that Kv4 channel subfamily members (either Kv4...
Carotid body type-I cells respond to acute hypoxia with membrane depolarization and calcium-dependent neurotransmitter release. The inhibition of a TASK-like background potassium channels plays a key role in initiating this response. Chronic hypoxia enhances the carotid body chemosensory responses evoked by acute hypoxia, however the accurate mechanism by which chronic hypoxia increases carotid...
Inhibition of K+ channels in glomus cells underlies excitation of the carotid body by hypoxia. It has recently been proposed that hypoxic inhibition involves either activation of AMP activated protein kinase (AMPK) or inhibition of carbon monoxide (CO) production by heme oxygenase 2 (HO-2). In the vasculature, L-type Ca2+ channels are also O2 sensitive. Here, we have investigated the possible involvement...
Polyamines modulate many biological functions. Here we report a novel inhibitory modulation by spermine of catecholamine release by the rat carotid body and have identified the molecular mechanism underpinning it. We used molecular (RT-PCR and confocal microscopy) and functional (i.e., neurotransmitter release, patch clamp recording and calcium imaging) approaches to test the involvement of: (i) voltage-dependent...
Mechanisms involved in carotid body (CB) chemoreceptor cells O2-sensing and responses are not fully understood. So far, it is known that hypoxia depolarizes chemoreceptor cells via O2-sensitive K+-channel inhibition; calcium influx via voltage-gated channels and neurotransmitter secretion follow. Presence of high voltage activated (HVA) calcium channels in rat CB chemoreceptor cells is well documented,...
The non-specific cAMP phosphodiesterase (PDE) inhibitor isobutyl- methylxanthine (IBMX) has been used to manipulate cAMP levels in carotid body (CB) preparations but the characterization of different PDE isoforms in CB has never been performed. PDE4 is one of the PDE families that uses cAMP as a specific substrate and changes its activity and affinity for drug inhibitors according to the degree of...
Calcium sensitivity of petrosal ganglion neurons (PGNs) to chemical stimuli with and without PC-12 cells in co-culture instead of glomus is not known– the idea being that two types of unusual cells could form synapse and provide a model for studies of chemotransduction. Calcium levels in the PGNs were measured in the presence of different chemical stimuli in the bath medium. Remarkably, the PGNs alone...
Quantitative real time PCR (qPCR) is a common tool used to compare the relative gene expression between treated/untreated cells, different types of tissues, or immature/mature organs. When homogeneous cells are used for qPCR, the Ct number of a tested gene solely represents the quantity of gene expression in cells. However, when a heterogeneous tissue is used for qPCR, the Ct number of a tested gene...
The carotid body (CB) is the main peripheral chemoreceptor. The present model of CB chemoreception states that glomus (type I) cells are the primary receptors, which are synaptically connected to the nerve terminals of the petrosal ganglion neurons. In response to hypoxia, hypercapnia and acidosis, glomus cells release one (or more) transmitter(s) which, acting on the nerve terminals of chemosensory...
In the present article we review in a concise manner the literature on the general biology of adenosine signalling. In the first section we describe briefly the historical aspects of adenosine research. In the second section is presented the biochemical characteristics of this nucleoside, namely its metabolism and regulation, and its physiological actions. In the third section we have succinctly...
We have recently demonstrated that adenosine controls the release of catecholamines (CA) from carotid body (CB) acting on A2B receptors. Here, we have investigated the hypothesis that this control is exerted via an interaction between adenosine A2B and dopamine D2 receptors present in chemoreceptor cells and if it is, the location of this interaction on the CB hypoxic transduction cascade. Experiments...
Benzodiazepines (BZs) suppress ventilation possibly by augmenting the GABAA receptor activity in the respiratory control system, but precise sites of action are not well understood. The goals of this study were: (1) to identify GABAA receptor subunits in the carotid body (CB) and petrosal ganglion (PG); (2) to test if BZs exert their effects through the GABAA receptor in the CB chemosensory unit....
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