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Mol. Cells 2010; 30(3): 245-253

Published online September 30, 2010

https://doi.org/10.1007/s10059-010-0117-9

© The Korean Society for Molecular and Cellular Biology

Quercetin Enhances Human α7 Nicotinic Acetylcholine Receptor-Mediated Ion Current through Interactions with Ca2+ Binding Sites

Byung-Hwan Lee4, Sun-Hye Choi4, Tae-Joon Shin4, Mi Kyung Pyo, Sung-Hee Hwang, Bo-Ra Kim, Sang-Mok Lee, Jun-Ho Lee1, Hyoung-Chun Kim2, Hye-Young Park3, Hyewhon Rhim3, and Seung-Yeol Nah*

Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Korea, 1Depart-ment of Physiology, College of Oriental Medicine, Kyung-Hee University, Seoul 130-701, Korea, 2Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Korea, 3Life Science Division, Korea Institute of Science and Technology, Seoul 136-791, Korea, 4These authors contributed equally to this work.

Correspondence to : *Correspondence: synah@konkuk.ac.kr

Received: April 20, 2010; Revised: June 10, 2010; Accepted: June 14, 2010

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.

Keywords α7 nAChR, Ca2+, Ca2+-binding site, flavonoids, quercetin

Article

Research Article

Mol. Cells 2010; 30(3): 245-253

Published online September 30, 2010 https://doi.org/10.1007/s10059-010-0117-9

Copyright © The Korean Society for Molecular and Cellular Biology.

Quercetin Enhances Human α7 Nicotinic Acetylcholine Receptor-Mediated Ion Current through Interactions with Ca2+ Binding Sites

Byung-Hwan Lee4, Sun-Hye Choi4, Tae-Joon Shin4, Mi Kyung Pyo, Sung-Hee Hwang, Bo-Ra Kim, Sang-Mok Lee, Jun-Ho Lee1, Hyoung-Chun Kim2, Hye-Young Park3, Hyewhon Rhim3, and Seung-Yeol Nah*

Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Korea, 1Depart-ment of Physiology, College of Oriental Medicine, Kyung-Hee University, Seoul 130-701, Korea, 2Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Korea, 3Life Science Division, Korea Institute of Science and Technology, Seoul 136-791, Korea, 4These authors contributed equally to this work.

Correspondence to:*Correspondence: synah@konkuk.ac.kr

Received: April 20, 2010; Revised: June 10, 2010; Accepted: June 14, 2010

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.

Keywords: α7 nAChR, Ca2+, Ca2+-binding site, flavonoids, quercetin

Mol. Cells
Jan 31, 2023 Vol.46 No.1, pp. 1~67
COVER PICTURE
RNAs form diverse shapes and play multiple functions as central molecules of gene expression. In this special issue on RNA, seven minireviews illustrate how basic concepts and recent RNA biology findings are transformed into new and exciting RNA therapeutics.

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