Quercetin enhances human α7 nicotinic acetylcholine receptor-mediated ion current through interactions with Ca2+ binding sites

Title
Quercetin enhances human α7 nicotinic acetylcholine receptor-mediated ion current through interactions with Ca2+ binding sites
Authors
이병환최선혜신태준표미경황성희김보라이상목이준호김형춘박혜원임혜원나승열
Keywords
α7 nAChR; Ca2+; Ca2+-binding site; flavonoids; quercetin
Issue Date
2010-09
Publisher
Molecules and cells
Citation
VOL 30, 245-253
Abstract
The flavonoid quercetin is a low molecular weight substance found in fruits and vegetables. Aside from its antioxidative effect, quercetin, like other flavonoids, has a wide range of neuropharmacological actions. The α7 nicotinic acetylcholine receptor (α7 nAChR) has a Ca2+-binding site, is highly permeable to the Ca2+ ion, and plays important roles in Ca2+-related normal brain functions. Dysfunctions of α7 nAChR are associated with a variety of neurological disorders. In the present study, we investigated the effects of quercetin on the ACh-induced inward peak current (IACh) in Xenopus oocytes that heterologously express human α7 nAChR. IACh was measured with the two-electrode voltage clamp technique. In oocytes injected with α7 nAChR cRNA, the effects of the co-application of quercetin on IACh were concentration-dependent and reversible. The ED50 was 36.1 + 6.1 μM. Quercetin-mediated enhancement of IACh caused more potentiation when quercetin was preapplied. The degree of IACh potentiation by quercetin preapplication was time-dependent and saturated after 1 min. Quercetin-mediated IACh enhancement was not affected by ACh concentration and was voltage-independent. However, quercetin-mediated IACh enhancement was dependent on extracellular Ca2+ concentrations and was specific to the Ca2+ ion, since the removal of extracellular Ca2+ or the addition of Ba2+ instead of Ca2+ greatly diminished quercetin enhancement of IACh. The mutation of Glu195 to Gln195, in the Ca2+-binding site, almost completely diminished quercetinmediated IACh enhancement. These results indicate that quercetin-mediated IACh enhancement human α7 nAChR heterologously expressed in Xenopus oocytes could be achieved through interactions with the Ca2+-binding site of the receptor.
URI
http://pubs.kist.re.kr/handle/201004/38024
ISSN
1016-8478
Appears in Collections:
KIST Publication > Article
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