Hydrogen sulfide as an oxygen sensor in trout gill chemoreceptors.
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.
Indiana University School of Medicine-South Bend, 1234 Notre Dame Ave., South Bend, IN 46617, USA. olson.1@nd.edu
Kenneth R
KR
Olson
Michael J
MJ
Healy
Zhaohong
Z
Qin
Nini
N
Skovgaard
Branka
B
Vulesevic
Douglas W
DW
Duff
Nathan L
NL
Whitfield
Guangdong
G
Yang
Rui
R
Wang
Steve F
SF
Perry
D000818:Animals; D002478:Cells, Cultured; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005880:Gills / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D006339:Heart Rate; D006862:Hydrogen Sulfide / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007267:Injections; D017736:Ion-Selective Electrodes; D008297:Male; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D046569:Neuroepithelial Cells / Q000378:metabolism; D017686:Oncorhynchus mykiss; D010100:Oxygen / Q000378:metabolism*; D011048:Polarography; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface; D012018:Reflex; D015656:Respiratory Mechanics; D015398:Signal Transduction / Q000187:drug effects; D015027:Zebrafish
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D010100:Oxygen; D006862:Hydrogen Sulfide