Resveratrol noncompetitively inhibits glycine receptor-mediated currents in neurons of rat central auditory neurons

Abstract

Resveratrol, a naturally occurring stilbene found in red wine, is known to modulate the activity of several types of ion channels and membrane receptors, including Ca²⁺, K⁺, and Na⁺ ion channels. However, little is known about the effects of resveratrol on some important receptors, such as glycine receptors and GABA_A receptors, in the central nervous system (CNS). In the present study, the effects of resveratrol on glycine receptor or GABA_A receptor-mediated currents in cultured rat inferior colliculus (IC) and auditory cortex (AC) neurons were studied using whole-cell voltage-clamp recordings. Resveratrol itself did not evoke any currents in IC neurons but it reversibly decreased the amplitude of glycine-induced current (I_Gly) in a concentration-dependent manner. Resveratrol did not change the reversal potential of I_Gly but it shifted the concentration-response relationship to the right without changing the Hill coefficient and with decreasing the maximum response of I_Gly. Interestingly, resveratrol inhibited the amplitude of I_Gly but not that of GABA-induced current (I_GABA) in AC neurons. More importantly, resveratrol inhibited GlyR-mediated but not GABA_AR-mediated inhibitory postsynaptic currents in IC neurons using brain slice recordings. Together, these results demonstrate that resveratrol noncompetitively inhibits I_Gly in auditory neurons by decreasing the affinity of glycine to its receptor. These findings suggest that the native glycine receptors but not GABA_A receptors in central neurons are targets of resveratrol during clinical administrations.

Keywords: Cell culture; GABA(A) receptor; Glycine receptor; Inferior colliculus; Resveratrol; Whole-cell patch-clamp.