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(2)S) 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(2)S scavenger and vitamin B(12) analog hydroxycobalamin (Cbl) as a new tool to investigate the involvement of endogenous H(2)S 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(2)S in cells. Based on its effects on the CB chemoreceptor cells we propose that endogenous H(2)S is an amplifier of the hypoxic transduction cascade which acts mainly by stimulating non-L-type Ca(2+) channels.