Effects of quercetin on α9α10 nicotinic acetylcholine receptor-mediated ion currents

Quercetin one of the flavonoids is a low molecular weight substance found in fruits and vegetables Quercetin like other flavonoids has a wide range of neuropharmacological actions and antioxidant effects The alpha 9 alpha 10 nicotinic acetylcholine receptor is one of the numerous nicotinic acetylcholine receptors that exist as a heteropentameric form between efferent olivocochlear fibers and hair cells of the cochlea In this study we report the effects of quercetin on rat alpha 9 alpha 10 nicotinic acetylcholine receptor mediated ion currents using the two-electrode voltage-clamp technique Treatment with acetylcholine evoked inward currents (I-ACh) in oocytes heterologously expressing the alpha 9 alpha 10 nicotinic acetylcholine receptor Quercetin blocked I-ACh in concentration-dependent and reversible manners and the blocking effect on I-ACh was stronger with pre-application than co-application of quercetin The half maximal inhibitory concentration (IC50) of quercetin was 45 4 +/- 10 1 mu M Quercetin mediated I-ACh inhibition was not affected by acetylcholine concentration and was independent of membrane-holding potential Although the inhibitory effect of quercetin was significantly attenuated in the absence of extracellular Ca2+ the action of quercetin was Independent of extracellular Ca2+ concentration indicating that the presence of extracellular Ca2+ might be needed for quercetin-related effects and might play an important role in quercetin-mediated regulation of the alpha 9 alpha 10 nicotinic acetylcholine receptor These results indicate that quercetin-mediated regulation of the alpha 9 alpha 10 nicotinic acetylcholine receptor could provide a molecular basis for quercetin actions at the cellular level (C) 2010 Elsevier B V All rights reserved