Hydrogen Sulfide as Endothelium-Derived Hyperpolarizing Factor Sulfhydrates Potassium Channels

Title
Hydrogen Sulfide as Endothelium-Derived Hyperpolarizing Factor Sulfhydrates Potassium Channels
Author(s)
정성미Snyder, Solomon H[Snyder, Solomon H]Mustafa, Asif K.[Mustafa, Asif K.]Sikka, Gautam[Sikka, Gautam]Gazi, Sadia K.[Gazi, Sadia K.]Steppan, Jochen[Steppan, Jochen]Bhunia, Anil K[Bhunia, Anil K]Barodka, Viachaslau M[Barodka, Viachaslau M]Gazi, Farah K[Gazi, Farah K]Barrow, Roxanne K[Barrow, Roxanne K]
Keywords
ARTERIAL SMOOTH-MUSCLE; NITRIC-OXIDE SYNTHASE; PERFORMANCE LIQUID-CHROMATOGRAPHY; CYSTATHIONINE GAMMA-LYASE; K-ATP CHANNELS; DEPENDENT RELAXATIONS; KNOCKOUT MICE; GAP-JUNCTIONS; BRAIN-TISSUE; RATS
Issue Date
201111
Publisher
LIPPINCOTT WILLIAMS & WILKINS
Citation
CIRCULATION RESEARCH, v.109, no.11, pp.1259 - U169
Abstract
Rationale: Nitric oxide, the classic endothelium-derived relaxing factor (EDRF), acts through cyclic GMP and calcium without notably affecting membrane potential. A major component of EDRF activity derives from hyperpolarization and is termed endothelium-derived hyperpolarizing factor (EDHF). Hydrogen sulfide (H(2)S) is a prominent EDRF, since mice lacking its biosynthetic enzyme, cystathionine gamma-lyase (CSE), display pronounced hypertension with deficient vasorelaxant responses to acetylcholine. Objective: The purpose of this study was to determine if H(2)S is a major physiological EDHF. Methods and Results: We now show that H(2)S is a major EDHF because in blood vessels of CSE-deleted mice, hyperpolarization is virtually abolished. H(2)S acts by covalently modifying (sulfhydrating) the ATP-sensitive potassium channel, as mutating the site of sulfhydration prevents H(2)S-elicited hyperpolarization. The endothelial intermediate conductance (IK(Ca)) and small conductance (SK(Ca)) potassium channels mediate in part the effects of H(2)S, as selective IK(Ca) and SK(Ca) channel inhibitors, charybdotoxin and apamin, inhibit glibenclamide-insensitive, H(2)S-induced vasorelaxation. Conclusions: H(2)S is a major EDHF that causes vascular endothelial and smooth muscle cell hyperpolarization and vasorelaxation by activating the ATP-sensitive, intermediate conductance and small conductance potassium channels through cysteine S-sulfhydration. Because EDHF activity is a principal determinant of vasorelaxation in numerous vascular beds, drugs influencing H(2)S biosynthesis offer therapeutic potential. (Circ Res. 2011; 109: 1259-1268.)
URI
http://hdl.handle.net/YU.REPOSITORY/24296http://dx.doi.org/10.1161/CIRCRESAHA.111.240242
ISSN
0009-7330
Appears in Collections:
의과대학 > 마취통증의학교실 > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE