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Title: Quercetin subunit specifically reduces glyr-mediated current in rat hippocampal neurons
Author: Sun, Hao ; Cheng, Xin-Ping ; Zeng, You-Ye ; Jiang, Peng ; Zhoua, Jiang-Ning
Source: NEUROSCIENCE
Issued Date: 2007
Volume: 148, Issue:2, Pages:548-559
Keyword: flavonoid ; glycine receptor ; whole-cell patch-clamp ; recording ; desensitization ; hippocampus ; GLYCINE RECEPTOR ; MESSENGER-RNAS ; BENZODIAZEPINE RECEPTOR ; DIETARY FLAVONOIDS ; CHLORIDE CHANNELS ; GINKGO-BILOBA ; SPINAL-CORD ; BRAIN ; GABA ; LOCALIZATION
Subject: Neurosciences & Neurology
Corresponding Author: Zhoua, JN (reprint author), Univ Sci & Technol China, Sch Life Sci, Dept Neurobiol & Biophys, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Anhui, Peoples R China,jnzhou@ustc.edu.cn
English Abstract: Quercetin is a substance of low molecular weight found in vascular plants with a wide range of biological activities including antioxidative and anti-inflammatory activities. In the present study, the effects of quercetin on native glycine receptors (GlyRs) in cultured rat hippocampal neurons were investigated using a whole-cell patch-clamp technique. Quercetin reversibly and concentration-dependently depressed glycine-induced current (I-Gly), with an IC50 of 10.7 +/- 0.24 AM and a Hill coefficient of 1.08 +/- 0.12. Quercetin depressed maximum I-Gly and significantly changed the EC50 for glycine and the Hill coefficient. Kinetic analysis indicated that quercetin accelerated the rates of desensitization. Interestingly, after the end of glycine with quercetin coapplication, a transient rebound occurred. The quercetin effects also displayed voltage-dependence, being greater at positive membrane potentials. These effects suggested that quercetin may act as an open channel blocker. Furthermore, in the sequential application protocol, quercetin inhibited the peak amplitude of I-Gly to a macroscopic degree while slowing GlyR desensitization. These effects implied that quercetin has a depressant effect independent of GlyR channel's opening, which maybe caused by an allosteric mechanism. Strikingly, quercetin inhibited the amplitude of recombinant-induced current mediated by alpha 2-, alpha 2 beta-, alpha 3- and alpha 3 beta-GlyRs but had no effects on alpha 1- and alpha 1 beta-GlyRs that were expressed in HEK293T cells. We also investigated the effects of quercetin on I-Gly in spinal neurons during development in vitro. The extent of blockade by quercetin on I-Gly was slighter in spinal neurons than in hippocampal neurons in a development-dependent manner. Taken together, our results suggest that quercetin has possible effects in information processing within a neuronal network by inhibition of I-Gly and may be useful as a pharmacological probe for identifying the subunit types of GlyRs. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1755
Appears in Collections:神经所(总)_期刊论文

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Sun, Hao; Cheng, Xin-Ping; Zeng, You-Ye; Jiang, Peng; Zhoua, Jiang-Ning.Quercetin subunit specifically reduces glyr-mediated current in rat hippocampal neurons,NEUROSCIENCE,2007,148(2):548-559
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