Hydrogen sulfide as an oxygen sensor in trout gill chemoreceptors

Abstract

O2 chemoreceptors elicit cardiorespiratory reflexes in all vertebrates, but consensus on O2-sensing signal transduction mechanism(s) is lacking. We recently proposed that hydrogen sulfide (H2S) metabolism is involved in O2 sensing in vascular smooth muscle. Here, we examined the possibility that H2S is an O2 sensor in trout chemoreceptors where the first pair of gills is a primary site of aquatic O2 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 O2, whereas mitochondrial H2S consumption was O2 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 approximately 10-mV depolarization. These studies are consistent with H2S involvement in O2 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, O2 sensor in a variety of tissues.

Hydrogen sulfide as an oxygen sensor

“…In rat tissues, O 2 either inhibits H 2 S production or it may be associated with H 2 S consumption and both are reversed by hypoxia (30,44). Similar observations have been made in a variety of tissues from numerous vertebrates (32,89,94,126,128,186). A compelling argument for H 2 S-mediated O 2 sensing can be made by comparing bovine and sea lion lungs.…”

“…Although removal of the first pair of gill arches, the site of peripheral chemoreceptors in the rainbow trout, inhibited hypoxic bradycardia, it did not affect hypoxic hyperventilation, nor did addition of the CBS inhibitor, AOA, or the CSE inhibitor, PPG (126). This suggests that fish have central chemoreceptors as well; however, it remains to be determined whether H 2 S signaling is involved.…”

“…Although high levels of H 2 S inhibit respiration, an intravascular injection or inhalation of lower concentrations of H 2 S mimics hypoxic hyperventilation in fish (126), birds (77), and mammals (7, 53, 55-57, 141, 175). These effects appear to be mediated through both central and peripheral mechanisms.…”

“…This suggests that fish have central chemoreceptors as well; however, it remains to be determined whether H 2 S signaling is involved. H 2 S stimulates peripheral chemoreceptors (NEC) in the trout gill, and this mediates hypoxic bradycardia (126). H 2 S also depolarizes NEC isolated from zebrafish gills, as does hypoxia.…”

GYY4137, a Novel Water-Soluble, H2S-Releasing Molecule

“…Interestingly, many of these effects of H 2 S in biological systems are not restricted to mammalian species. For example, biosynthesis of this gas has been detected in the tissues from organisms found across several taxonomic kingdoms (Calderwood & Kopriva, 2014;Clarke, 1953;Julian, Statile, Wohlgemuth, & Arp, 2002;Olson et al, 2008;Papenbrock, Riemenschneider, Kamp, Schulz-Vogt, & Schmidt, 2007). In the plant kingdom, exogenous application of H 2 S has been reported to increase crop yields, germination rates, influence root development, and alleviate heavy metal ion induced stress responses (Calderwood & Kopriva, 2014;Lisjak, Teklic, Wilson, Whiteman, & Hancock, 2013).…”