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, Hyewhon Nah, Seung-Yeol 2024-01-20T18:34:16Z 2024-01-20T18:34:16Z 2021-09-05 2010-09 1016-8478 https://pubs.kist.re.kr/handle/201004/131148 The flavonoid quercetin is a low molecular weight substance found in fruits and vegetables. Aside from its anti-oxidative effect, quercetin, like other flavonoids, has a wide range of neuropharmacological actions. The alpha 7 nicotinic acetylcholine receptor (alpha 7 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 alpha 7 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 (I-ACh) in Xenopus oocytes that heterologously express human alpha 7 nAChR. I-ACh was measured with the two-electrode voltage clamp technique. In oocytes injected with alpha 7 nAChR cRNA, the effects of the co-application of quercetin on I-ACh were concentration-dependent and reversible. The ED50 was 36.1 + 6.1 mu M. Quercetin-mediated enhancement of I-ACh caused more potentiation when quercetin was pre-applied. The degree of I-ACh potentiation by quercetin pre-application was time-dependent and saturated after 1 min. Quercetin-mediated I-ACh enhancement was not affected by ACh concentration and was voltage-independent. However, quercetin-mediated I-ACh 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 I-ACh. The mutation of Glu195 to Gln195, in the Ca2+-binding site, almost completely diminished quercetin-mediated I-ACh enhancement. These results indicate that quercetin-mediated I-ACh enhancement human alpha 7 nAChR heterologously expressed in Xenopus oocytes could be achieved through interactions with the Ca2+-binding site of the receptor. English KOREAN SOC MOLECULAR & CELLULAR BIOLOGY HIGH-CALCIUM PERMEABILITY CHANNEL DOMAIN MOLECULAR-CLONING AGONIST-BINDING XENOPUS OOCYTES MUTATIONS NEURONS SUBUNIT FAMILY GENE Quercetin Enhances Human alpha 7 Nicotinic Acetylcholine Receptor-Mediated Ion Current through Interactions with Ca2+ Binding Sites Article 10.1007/s10059-010-0117-9 1 MOLECULES AND CELLS, v.30, no.3, pp.245 - 253 MOLECULES AND CELLS 30 3 245 253 scie scopus kci ART001488343 000282232200009 2-s2.0-78049318379 Biochemistry & Molecular Biology Cell Biology Biochemistry & Molecular Biology Cell Biology Article HIGH-CALCIUM PERMEABILITY CHANNEL DOMAIN MOLECULAR-CLONING AGONIST-BINDING XENOPUS OOCYTES MUTATIONS NEURONS SUBUNIT FAMILY GENE alpha 7 nAChR Ca2+ Ca2+-binding site flavonoids quercetin