Hydroxycobalamin Reveals the Involvement of Hydrogen Sulfide in the Hypoxic Responses of Rat Carotid Body Chemoreceptor Cells

Carotid body (CB) chemoreceptor cells sense arterial blood PO 2, generating a neurosecretory response proportional to the intensity of hypoxia. Hydrogen sulfide (H 2S) 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 H 2S scavenger and vitamin B 12 analog hydroxycobalamin (Cbl) as a new tool to investigate the involvement of endogenous H 2S 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 [Ca 2+] i evoked by 50 μM NaHS in enzymatically dispersed CB glomus cells. Moreover, Cbl markedly inhibited the catecholamine release and [Ca 2+] 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 Ca 2+ channel blocker nifedipine slightly inhibited the rise in CB chemoreceptor cells [Ca 2+] i elicited by sulfide, whilst causing a somewhat larger attenuation of the hypoxia-induced Ca 2+ signal. We conclude that Cbl is a useful and specific tool for studying the function of H 2S in cells. Based on its effects on the CB chemoreceptor cells we propose that endogenous H 2S is an amplifier of the hypoxic transduction cascade which acts mainly by stimulating non-L-type Ca 2+ channels. View Full-Tex