Abstract
Carotid body (CB) chemoreceptor cells sense arterial blood PO2, generating a neurosecretory response proportional to the intensity of hypoxia. Hydrogen sulfide (H2S) is a physiological gaseous messenger that is proposed to act as an oxygen sensor in CBs, although this concept remains controversial. In the present study we have used the H2S scavenger and vitamin B12 analog hydroxycobalamin (Cbl) as a new tool to investigate the involvement of endogenous H2S in CB oxygen sensing. We observed that the slow-release sulfide donor GYY4137 elicited catecholamine release from isolated whole carotid bodies, and that Cbl prevented this response. Cbl also abolished the rise in [Ca2+]i evoked by 50 µM NaHS in enzymatically dispersed CB glomus cells. Moreover, Cbl markedly inhibited the catecholamine release and [Ca2+]i rise caused by hypoxia in isolated CBs and dispersed glomus cells, respectively, whereas it did not alter these responses when they were evoked by high [K+]e. The L-type Ca2+ channel blocker nifedipine slightly inhibited the rise in CB chemoreceptor cells [Ca2+]i elicited by sulfide, whilst causing a somewhat larger attenuation of the hypoxia-induced Ca2+ signal. We conclude that Cbl is a useful and specific tool for studying the function of H2S in cells. Based on its effects on the CB chemoreceptor cells we propose that endogenous H2S is an amplifier of the hypoxic transduction cascade which acts mainly by stimulating non-L-type Ca2+ channels.
Highlights
The carotid bodies (CB), located in the vicinity of the carotid artery bifurcations, are formed by clusters of two types of parenchymatous cells, chemoreceptor and sustentacular
In order to further characterize the potential physiological significance of endogenously generated sulfide, in the present study we describe for the first time the use of the hydroxyl form of vitamin B12 or hydroxycobalamin as a new tool for studying the role of sulfide as a mediator of cell responses
Effects of Cbl on the Release of 3 H-CA Induced by Hydrogen Sulfide Donors
Summary
The carotid bodies (CB), located in the vicinity of the carotid artery bifurcations, are formed by clusters of two types of parenchymatous cells, chemoreceptor and sustentacular. Cell clusters are surrounded by a dense net of capillaries and penetrated by sensory nerve endings of the carotid sinus nerve (CSN) which form synaptic contacts with chemoreceptor cells; the soma of CSN fibres are located in the petrosal ganglion and project centrally to the nucleus tractus solitarius. Chemoreceptor cells sense the PO2 , PCO2 , and pH from nearby capillaries, becoming activated when PO2 decreases and/or PCO2 /[H+ ] increases. The chemoreceptor cell mechanisms linking the presentation of the stimulus to the activation of the exocytotic release of neurotransmitters, i.e., the sensory transduction cascades, are not fully understood. A commonly accepted transduction cascade for hypoxia consists of the following steps: detection of hypoxia by an oxygen sensor → coupling of the sensor to oxygen-sensitive K+ channels →
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