Inhibitory influence of ginsenoside Rb 3 on activation of strychnine-sensitive glycine receptors in hippocampal neurons of rat

Abstract

Whole-cell patch-clamp technique was used to investigate the effect of ginsenoside Rb 3 (Rb 3), an active constituent of Panax ginseng, on glycine receptor activity in immature hippocampal neurons, which were dissociated acutely from hippocampal CA 1 area in Sprague–Dawley rats aging 10–14 days using the method of enzyme digestion with mechanical dissociation. As a result, glycine elicited an inward current ( I gly) in a concentration-dependent manner in approximately 86% of those isolated neurons tested. This current was strychnine-sensitive. Rb 3 itself did not elicit any membrane currents. However, coapplication of Rb 3 inhibited peak current of I gly. This depressant effect of Rb 3 varied with its concentrations. At a concentration of 0.1 μmol/L, ginsenoside Rb 3 had the most significant inhibition, with a net reduction of 31% in average. Moreover, the inhibition of I gly by Rb 3 did not depend on the membrane potential. Rb 3 (0.1 μmol/L) presented inhibitory effect on I gly mainly at higher glycine concentrations (>100 μmol/L), and decreased maximal glycine efficacy. This effect was the same as that of a non-competitive antagonist of glycine receptors. Finally, we found that Rb 3 prolonged the time constant of activation of I gly. It is therefore suggested that ginsenoside Rb 3, possibly as a non-competitive antagonist, could inhibit strychnine-sensitive glycine current at a dose-dependent manner in acutely dissociated hippocampal CA 1 neurons of young rats, and decrease of affinity of glycine to receptors and delay of receptor activation may be involved in this inhibition. Inhibitory effect of ginsenoside Rb 3 on I gly is possibly one of the bases of many pharmacological actions of Panax ginseng.