Endogenous H2S is required for hypoxic sensing by carotid body glomus cells

Vladislav V. Makarenko, Jayasri Nanduri, Gayatri Raghuraman, Aaron P. Fox, Moataz M. Gadalla, Ganesh K. Kumar, Solomon H. Snyder, Nanduri R. Prabhakar

Research output: Contribution to journalArticlepeer-review

Abstract

H2S generated by the enzyme cystathionine-γ-lyase (CSE) has been implicated in O2 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 H2S in an O2-sensitive manner and whether endogenous H2S is required for O2 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 (PO2 ~30 mmHg) increased H2S 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 H2S donor (50 μM NaHS) increased cytosolic Ca2+ concentration ([Ca2+]i) in glomus cells, with a time course and magnitude that are similar to that produced by hypoxia. [Ca2+]i responses to NaHS and hypoxia were markedly attenuated in the presence of Ca2+-free medium or cadmium chloride, a pan voltage-gated Ca2+ channel blocker, or nifedipine, an L-type Ca2+ channel inhibitor, suggesting that both hypoxia and H2S share common Ca2+-activating mechanisms. These results demonstrate that H2S generated by CSE is a physiologic mediator of the glomus cell's response to hypoxia.

Original languageEnglish (US)
Pages (from-to)C916-C923
JournalAmerican Journal of Physiology - Cell Physiology
Volume303
Issue number9
DOIs
StatePublished - Nov 1 2012

Keywords

  • Arterial chemoreceptors
  • Breathing
  • Gasotransmitters
  • O sensing
  • Voltage-gated Cachannels

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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