Resveratrol Inhibits GABA<SUB>C</SUB> &#1361; Receptor-Mediated Ion Currents Expressed in Xenopus Oocytes

Resveratrol Inhibits GABA<SUB>C</SUB> &#1361; Receptor-Mediated Ion Currents Expressed in Xenopus Oocytes

Resveratrol is a phytoalexin found in grapes, red wine, and berries. Resveratrol has been known to have many beneficial health effects, such as anti-cancer, neuroprotective, anti-inflammatory, and life-prolonging effects. However, relatively little is known about the effects of resveratrol on the regulation of ligand-gated ion channels. We have previously reported that resveratrol regulates subsets of homomeric ligand-gated ion channels such as those of 5-HT_3A receptors. The &#1347;-aminobutyric acid_C (GABA_C) receptor is mainly expressed in retinal bipolar cells and plays an important role in visual processing. In the present study, we examined the effects of resveratrol on the channel activity of homomeric GABA_C receptor expressed in Xenopus oocytes injected with cRNA encoding human GABA_C &#1361; subunits. Our data show that the application of GABA elicits an inward peak current (I_GABA) in oocytes that express the GABA_C receptor. Resveratrol treatment had no effect on oocytes injected with H₂O or with GABA_C receptor cRNA. Co-treatment with resveratrol and GABA inhibited I_GABA in oocytes with GABA_C receptors. The inhibition of I_GABA by resveratrol was in a reversible and concentration-dependent manner. The IC₅₀ of resveratrol was 28.9±2.8 &#1356;M in oocytes expressing GABA_C receptor. The inhibition of I_GABA by resveratrol was in voltage-independent and non-competitive manner. These results indicate that resveratrol might regulate GABA_C receptor expression and that this regulation might be one of the pharmacological actions of resveratrol on the nervous system.