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