Quercetin enhances human α7 nicotinic acetylcholine receptor-mediated ion current through interactions with Ca(2+) binding sites.
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 Ca(2+)-binding site, is highly permeable to the Ca(2+) ion, and plays important roles in Ca(2+)-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 ED(50) 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 Ca(2+) concentrations and was specific to the Ca(2+) ion, since the removal of extracellular Ca(2+) or the addition of Ba(2+) instead of Ca(2+) greatly diminished quercetin enhancement of I(ACh). The mutation of Glu195 to Gln195, in the Ca(2+)-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 Ca(2+)-binding site of the receptor.
Lee
Byung-Hwan
BH
Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, 143-701, Korea.
Choi
Sun-Hye
SH
Shin
Tae-Joon
TJ
Pyo
Mi Kyung
MK
Hwang
Sung-Hee
SH
Kim
Bo-Ra
BR
Lee
Sang-Mok
SM
Lee
Jun-Ho
JH
Kim
Hyoung-Chun
HC
Park
Hye-Young
HY
Rhim
Hyewhon
H
Nah
Seung-Yeol
SY
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D003001:Cloning, Molecular; D006801:Humans; D017136:Ion Transport / Q000187:drug effects* / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D009865:Oocytes; D011794:Quercetin / Q000008:administration & dosage*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics; D014981:Xenopus; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D011794:Quercetin; D002118:Calcium