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Novel expression of a functional glycine receptor chloride channel that attenuates contraction in airway smooth muscle
Author(s) -
Yim Peter D.,
Gallos George,
Xu Dingbang,
Zhang Yi,
Emala Charles W.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-170530
Subject(s) - glycine receptor , strychnine , chloride channel , chemistry , glycine , contraction (grammar) , guinea pig , muscle relaxation , muscle contraction , agonist , endocrinology , biophysics , medicine , receptor , biochemistry , amino acid , biology
Airway smooth muscle (ASM) contraction is an important component of the pathophysiology of asthma. Taurine, an agonist of glycine receptor chloride (GlyR Cl − ) channels, was found to relax contracted ASM, which led us to question whether functional GlyR Cl − channels are expressed in ASM. Messenger RNA for β (GLRB), cd (GLRA1), α2 (GLRA2), and α.4 (GLRA4) subunits were found in human ( Homo sapiens ) and guinea pig ( Cavia porcellus ) tracheal smooth muscle. Immunoblotting confirmed the protein expression of GLRA1 and GLRB subunits in ASM. Electrical activity of cultured human ASM cells was assessed using a fluorescent potentiometric dye and electrophysiological recordings. Glycine increased current and significantly increased fluorescence in a dose‐dependent manner. The GlyR Cl − channel antagonist strychnine significantly blocked the effects of glycine on potentiometric fluorescence in ASM cells. Guinea pig airway ring relaxation of ACh‐induced contractions by isoproterenol was significantly left‐shifted in the presence of glycine. This effect of glycine was blocked by pretreatment with the GlyR Cl − channel antagonist strychnine. Glycine treatment during tachykinin‐ and acetylcholine‐induced contractions significantly decreased the maintenance of muscle force compared to control. GlyR Cl − channels are expressed on ASM and regulate smooth muscle force and offer a novel target for therapeutic relaxation of ASM.—Yim, P. D., Gallos, G., Xu, D., Zhang, Y., Emala, C. W. Novel expression of a functional glycine receptor chloride channel that attenuates contraction in airway smooth muscle. FASEB J. 25, 1706–1717 (2011). www.fasebj.org