Document Detail


A crucial role for hydrogen sulfide in oxygen sensing via modulating large conductance calcium-activated potassium channels.
MedLine Citation:
PMID:  19803741     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hydrogen sulfide (H(2)S) is an important signaling molecule produced from L-cysteine by cystathionine beta-synthetase (CBS) or cystathionine gamma-lyase (CSE). Here we examined the role of H(2)S in the oxygen-sensing function of the carotid body chemoreceptors, where the large conductance Ca(2+)-activated potassium channel (BK(Ca)) plays a key role. In the isolated mouse carotid body/sinus nerve preparations, the H(2)S donor, NaHS, excited the chemoreceptor afferent nerves in a concentration-dependent manner that was reversed by carbon monoxide donor. The NaHS-evoked excitation was abolished by removing extracellular Ca(2+), or using Cd(2+), pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid and hexomethonium, suggesting that H(2)S evokes release of ATP/ACh from type I glomus cells of the carotid body. The chemoreceptor afferent activation by hypoxia was decreased remarkably using CBS inhibitors, amino oxyacetic acid (AOAA) and hydroxylamine, but not CSE inhibitors, propargylglycine and beta-cyano-L-alanine, despite expression of both enzymes in type I glomus cells. In these cells, the BK(Ca) currents were inhibited by hypoxia and such inhibition was mimicked by NaHS and diminished by AOAA. Finally, mice hyperventilated in response to hypoxia, which was prevented by CBS inhibitors. These data suggest that H(2)S plays a crucial role in mediating the response of carotid body chemoreceptors to hypoxia via modulating the BK(Ca) channels.
Authors:
Qian Li; Biying Sun; Xiaofang Wang; Zhu Jin; Yun Zhou; Li Dong; Lin-Hua Jiang; Weifang Rong
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  12     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-13     Completed Date:  2010-06-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1179-89     Citation Subset:  IM    
Affiliation:
Department of Physiology, Shanghai Jiaotong University School of Medicine, Shanghai, China.
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MeSH Terms
Descriptor/Qualifier:
Afferent Pathways / physiology
Air Pollutants / metabolism
Animals
Anoxia / metabolism
Carbon Monoxide / metabolism
Carotid Body / cytology,  metabolism*
Chemoreceptor Cells / cytology,  metabolism
Hydrogen Sulfide / metabolism*
Large-Conductance Calcium-Activated Potassium Channels / genetics,  metabolism*
Mice
Oxygen / metabolism*
Patch-Clamp Techniques
Plethysmography, Whole Body
Chemical
Reg. No./Substance:
0/Air Pollutants; 0/Large-Conductance Calcium-Activated Potassium Channels; 630-08-0/Carbon Monoxide; 7782-44-7/Oxygen; 7783-06-4/Hydrogen Sulfide

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