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 α9α10 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 α9α10 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 α9α10 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 (IC(50)) of quercetin was 45.4±10.1μM. 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 Ca(2+), the action of quercetin was independent of extracellular Ca(2+) concentration, indicating that the presence of extracellular Ca(2+) might be needed for quercetin-related effects and might play an important role in quercetin-mediated regulation of the α9α10 nicotinic acetylcholine receptor. These results indicate that quercetin-mediated regulation of the α9α10 nicotinic acetylcholine receptor could provide a molecular basis for quercetin actions at the cellular level.
Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea.
Byung-Hwan
BH
Lee
Sun-Hye
SH
Choi
Tae-Joon
TJ
Shin
Mi Kyung
MK
Pyo
Sung-Hee
SH
Hwang
Sang-Mok
SM
Lee
Hyun-Dong
HD
Paik
Hyoung-Chun
HC
Kim
Seung-Yeol
SY
Nah
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004553:Electric Conductivity; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D007477:Ions / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*
D007477:Ions; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D011794:Quercetin; D002118:Calcium