Carotid body oxygen sensing

Abstract

The carotid body (CB) is a neural crest-derived organ whose major function is to sense changes in arterial oxygen tension to elicit hyperventilation in hypoxia. The CB is composed of clusters of neuron-like glomus, or type-I, cells enveloped by glia-like sustentacular, or type-II, cells. Responsiveness of CB to acute hypoxia relies on the inhibition of O 2 -sensitive K + channels in glomus cells, which leads to cell depolarisation, Ca 2+ entry and release of transmitters that activate afferent nerve fibres. Although this model of O 2 sensing is generally accepted, the molecular mechanisms underlying K + channel modulation by O 2 tension are unknown. Among the putative hypoxia-sensing mechanisms there are: the production of oxygen radicals, either in mitochondria or reduced nicotinamide adenine dinucleotide phosphate oxidases; metabolic mitochondrial inhibition and decrease of intracellular ATP; disruption of the prolylhydroxylase/ hypoxia inducible factor pathway; or decrease of carbon monoxide production by haemoxygenase-2. In chronic hypoxia, the CB grows with increasing glomus cell number. The current authors have identified, in the CB, neural stem cells, which can differentiate into glomus cells. Cell fate experiments suggest that the CB progenitors are the glia-like sustentacular cells. The CB appears to be involved in the pathophysiology of several prevalent human diseases.

Behavioral Responses to Hypoxia in Drosophila Larvae Are Mediated by Atypical Soluble Guanylyl Cyclases

“…In addition, animals also show short-term responses to hypoxia that occur in a time frame of seconds or minutes and likely do not involve transcription-mediated events. The mammalian carotid body is a peripheral chemoreceptor that senses a number of blood-borne stimuli, including hypoxia and hypercapnia, transducing them into neural discharges that initiate a number of cardiorespiratory reflexes (Gonzalez et al 1994;Ló pez-Barneo et al 2008). Both long-term and short-term responses to hypoxia critically depend on the ability to detect decreases in O 2 supply; however, the molecular bases for O 2 -sensing systems have only recently begun to be identified (Gray et al 2004;Morton 2004b;Vermehren et al 2006).…”

Immunohistochemical Localization of Some Neurotrophic Factors and Their Receptors in the Rat Carotid Body

“…This functional maturation partially depends on structural and neurochemical changes, which are promoted by some neurotransmitters, trophic factors and their receptors, acting on the CB cell population in autocrine or paracrine ways [6][7][8]. Besides, there is a convincing evidence that neurotrophic factors from CB cells and nerve fibers also play an important role in maintaining the structural and functional specialization of both CB components in adulthood [9].…”

Sources of Inspiration: A Neurophysiologic Framework for Understanding Anesthetic Effects on Ventilatory Control

“…The carotid bodies are neural-crest-derived structures located at the carotid bifurcations, deriving their substantial blood supply (the highest blood flow per unit of mass of any organ in the body) from the external carotid arteries [26]. The carotid body glomus cells respond to the P a O 2 rather than the oxygen saturation.…”

“…The glomus cells then behave as presynaptic neurons, releasing neurotransmitter vesicles to trigger action potentials in nearby afferent terminals from the carotid sinus branch of cranial nerve IX. The action potentials travel via this nerve to the nucleus of the tractus solitarius, the major sensory input terminal of the medulla, where they depolarize interneurons, which synapse with the preBOTc [26]. The primary effect of hypoxemia is to increase the gain of the ventilatory response to CO 2 rather than to serve as a primary ventilatory control mechanism [27].…”