Hydrogen sulfide as an oxygen sensor in trout gill chemoreceptors

[O.sub.2] chemoreceptors elicit cardiorespiratory reflexes in all vertebrates, but consensus on [O.sub.2]-sensing signal transduction mechanism(s) is lacking. We recently proposed that hydrogen sulfide ([H.sub.2]S) metabolism is involved in [O.sub.2] sensing in vascular smooth muscle. Here, we examined the possibility that [H.sub.2]S is an [O.sub.2] sensor in trout chemoreceptors where the first pair of gills is a primary site of aquatic [O.sub.2] sensing and the homolog of the mammalian carotid body. Intrabuccal injection of [H.sub.2]S in unanesthetized trout produced a dose-dependent bradycardia and increased ventilatory frequency and amplitude similar to the hypoxic response. Removal of the first, but not second, pair of gills significantly inhibited [H.sub.2]S-mediated bradycardia, consistent with the loss of aquatic chemoreceptors, mRNA for [H.sub.2]S-synthesizing enzymes, cystathionine [beta]-synthase and cystathionine [gamma]-lyase, was present in branchial tissue. Homogenized gills produced [H.sub.2]S enzymatically, and [H.sub.2]S production was inhibited by [O.sub.2], whereas mitochondrial [H.sub.2]S consumption was [O.sub.2] dependent. Ambient hypoxia did not affect plasma [H.sub.2]S in unanesthetized trout, but produced a [Po.sub.2]-dependent increase in a sulfide moiety suggestive of increased [H.sub.2]S production. In isolated zebrafish neuroepithelial cells, the putative chemoreceptive cells of fish, both hypoxia and [H.sub.2]S, produced a similar ~10-mV depolarization. These studies are consistent with [H.sub.2]S involvement in [O.sub.2] sensing/signal transduction pathway(s) in chemoreceptive cells, as previously demonstrated in vascular smooth muscle. This novel mechanism, whereby [H.sub.2]S concentration ([[H.sub.2]S]) is governed by the balance between constitutive production and oxidation, tightly couples tissue [[H.sub.2]S] to [Po.sub.2] and may provide an exquisitely sensitive, yet simple, [O.sub.2] sensor in a variety of tissues. hydrogen sulfide concentration