|
KMID : 0578320100300030245
|
|
Molecules and Cells
2010 Volume.30 No. 3 p.245 ~ p.253
|
|
|
Quercetin Enhances Human α7 Nicotinic Acetylcholine Receptor-Mediated Ion Current through Interactions with Ca2+ Binding Sites
|
|
Lee Byung-Hwan
Choi Sun-Hye
Shin Tae-Joon
Pyo Mi-Kyung
Hwang Sung-Hee
Kim Bo-Ra
Lee Sang-Mok
Lee Jun-Ho
Kim Hyoung-Chun
Park Hye-Young
Rhim Hye-Whon
Nah Seung-Yeol
|
|
|
Abstract
|
|
|
|
The flavonoid quercetin is a low molecular weight sub-stance 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-elec-trode 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 pre-applied. The degree of IACh potentiation by quercetin pre-application 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 enhance-ment 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 quercetin- mediated IACh enhancement. These results indicate that quercetin-mediated IACh enhancement human α7 nAChR heterologously ex-pressed in Xenopus oocytes could be achieved through interactions with the Ca2+-binding site of the receptor.
|
|
|
KEYWORD
|
|
|
α7 nAChR, Ca2+, Ca2+-binding site, flavonoids, quercetin
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|
|