Hydrogen sulfide as an oxygen sensor in trout gill chemoreceptors

O-2 chemoreceptors elicit cardiorespiratory reflexes in all vertebrates, but consensus on O-2-sensing signal transduction mechanism(s) is lacking. We recently proposed that hydrogen sulfide (H2S) metabolism is involved in O-2 sensing in vascular smooth muscle. Here, we examined the possibility that H2S is an O-2 sensor in trout chemoreceptors where the first pair of gills is a primary site of aquatic O-2 sensing and the homolog of the mammalian carotid body. Intrabuccal injection of H2S 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 H2S-mediated bradycardia, consistent with the loss of aquatic chemoreceptors. mRNA for H2S-synthesizing enzymes, cystathionine beta-synthase and cystathionine gamma-lyase, was present in branchial tissue. Homogenized gills produced H2S enzymatically, and H2S production was inhibited by O-2, whereas mitochondrial H2S consumption was O-2 dependent. Ambient hypoxia did not affect plasma H2S in unanesthetized trout, but produced a PO2-dependent increase in a sulfide moiety suggestive of increased H2S production. In isolated zebrafish neuroepithelial cells, the putative chemoreceptive cells of fish, both hypoxia and H2S, produced a similar similar to 10-mV depolarization. These studies are consistent with H2S involvement in O-2 sensing/signal transduction pathway( s) in chemoreceptive cells, as previously demonstrated in vascular smooth muscle. This novel mechanism, whereby H2S concentration ([H2S]) is governed by the balance between constitutive production and oxidation, tightly couples tissue [H2S] to PO2 and may provide an exquisitely sensitive, yet simple, O-2 sensor in a variety of tissues.