Ginsenoside Rg3 regulates GABAA receptor channel activity: Involvement of interaction with the γ2 subunit

Ginseng exhibits beneficial effects on GABAA receptor-related anxiety and sleep disorders. However, little is known regarding the cellular and molecular bases of the ginseng action on GABAA receptor. The present study was performed to elucidate the molecular mechanism of the ginseng effect on GABAA receptor. The effect of ginsenoside Rg3 (Rg3), one of the active ingredients of ginseng, on γ-aminobutyric acid (GABA)A receptor channel activity was examined in Xenopus oocytes using two-electrode voltage-clamp technique. Rg3 itself evoked an inward current in Xenopus oocytes expressing GABAA receptor subunits (α1β1γ2) and the Rg3 itself-elicited inward current was only selective to γ2 subunit expression ratio, since Rg3 alone had no effects in oocytes expressing other subunits such as γ1, γ3, δ, or ε. Co-treatment of Rg3 with GABA enhanced GABA receptor (α1β1γ2)-mediated inward currents (IGABA) but Rg3-mediated IGABA enhancement was independent on γ2. Rg3 itself-elicited inward current was blocked by GABAA receptor antagonist. The present results indicate that Rg3-induced GABAA receptor activation via the γ2 subunit and IGABA enhancement by Rg3 might be one of the molecular bases of ginseng effects on GABAA receptor.