title: Endogenous H2S is required for hypoxic sensing by carotid body glomus cells.
abstract: H(2)S generated by the enzyme cystathionine-γ-lyase (CSE) has been implicated in O(2) sensing by the carotid body. The objectives of the present study were to determine whether glomus cells, the primary site of hypoxic sensing in the carotid body, generate H(2)S in an O(2)-sensitive manner and whether endogenous H(2)S is required for O(2) sensing by glomus cells. Experiments were performed on glomus cells harvested from anesthetized adult rats as well as age and sex-matched CSE(+/+) and CSE(-/-) mice. Physiological levels of hypoxia (Po(2) ∼30 mmHg) increased H(2)S levels in glomus cells, and dl-propargylglycine (PAG), a CSE inhibitor, prevented this response in a dose-dependent manner. Catecholamine (CA) secretion from glomus cells was monitored by carbon-fiber amperometry. Hypoxia increased CA secretion from rat and mouse glomus cells, and this response was markedly attenuated by PAG and in cells from CSE(-/-) mice. CA secretion evoked by 40 mM KCl, however, was unaffected by PAG or CSE deletion. Exogenous application of a H(2)S donor (50 μM NaHS) increased cytosolic Ca(2+) concentration ([Ca(2+)](i)) in glomus cells, with a time course and magnitude that are similar to that produced by hypoxia. [Ca(2+)](i) responses to NaHS and hypoxia were markedly attenuated in the presence of Ca(2+)-free medium or cadmium chloride, a pan voltage-gated Ca(2+) channel blocker, or nifedipine, an L-type Ca(2+) channel inhibitor, suggesting that both hypoxia and H(2)S share common Ca(2+)-activating mechanisms. These results demonstrate that H(2)S generated by CSE is a physiologic mediator of the glomus cell's response to hypoxia.
authors: Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, Chicago, IL 60637, USA. nanduri@uchicago.edu
authors: Vladislav V
authors: VV
authors: Makarenko
authors: Jayasri
authors: J
authors: Nanduri
authors: Gayatri
authors: G
authors: Raghuraman
authors: Aaron P
authors: AP
authors: Fox
authors: Moataz M
authors: MM
authors: Gadalla
authors: Ganesh K
authors: GK
authors: Kumar
authors: Solomon H
authors: SH
authors: Snyder
authors: Nanduri R
authors: NR
authors: Prabhakar
mesh_terms: D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D019256:Cadmium Chloride / Q000494:pharmacology; D002118:Calcium / Q000032:analysis; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002344:Carotid Body / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000494:pharmacology
chemical_list: D000480:Alkynes; D002121:Calcium Channel Blockers; D002395:Catecholamines; D004791:Enzyme Inhibitors; D013440:Sulfides; C009055:propargylglycine; D011189:Potassium Chloride; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D009543:Nifedipine; D019256:Cadmium Chloride; D002118:Calcium; D005998:Glycine; D006862:Hydrogen Sulfide