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Quercetin enhances human α7 nicotinic acetylcholine receptor-mediated ion current through interactions with Ca2+ binding sites

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Molecules and Cells

Abstract

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 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 (I ACh ) in Xenopus oocytes that heterologously express human α7 nAChR. I ACh was measured with the two-electrode voltage clamp technique. In oocytes injected with α7 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 μM. 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 IACh. 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 α7 nAChR heterologously expressed in Xenopus oocytes could be achieved through interactions with the Ca2+-binding site of the receptor.

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Authors and Affiliations

  1. Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, 143-701, Korea

    Byung-Hwan Lee, Sun-Hye Choi, Tae-Joon Shin, Mi Kyung Pyo, Sung-Hee Hwang, Bo-Ra Kim, Sang-Mok Lee & Seung-Yeol Nah

  2. Department of Physiology, College of Oriental Medicine, Kyung-Hee University, Seoul, 130-701, Korea

    Jun-Ho Lee

  3. Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 200-701, Korea

    Hyoung-Chun Kim

  4. Life Science Division, Korea Institute of Science and Technology, Seoul, 136-791, Korea

    Hye-Young Park & Hyewhon Rhim

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  1. Byung-Hwan Lee
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  2. Sun-Hye Choi
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Correspondence to Seung-Yeol Nah.

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Lee, BH., Choi, SH., Shin, TJ. et al. Quercetin enhances human α7 nicotinic acetylcholine receptor-mediated ion current through interactions with Ca2+ binding sites. Mol Cells 30, 245–253 (2010). https://doi.org/10.1007/s10059-010-0117-9

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