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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
Sep 30, 2022 Vol.45 No.9, pp. 603~672
COVER PICTURE
The Target of Rapamycin Complex (TORC) is a central regulatory hub in eukaryotes, which is well conserved in diverse plant species, including tomato (Solanum lycopersicum). Inhibition of TORC genes (SlTOR, SlLST8, and SlRAPTOR) by VIGS (virus-induced gene silencing) results in early fruit ripening in tomato. The red/ orange tomatoes are early-ripened TORC-silenced fruits, while the green tomato is a control fruit. Top, left, control fruit (TRV2-myc); top, right, TRV2-SlLST8; bottom, left, TRV2-SlTOR; bottom, right, TRV2-SlRAPTOR(Choi et al., pp. 660-672).

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