Effects of EGCG on voltage-gated sodium channels in primary cultures of rat hippocampal CA1 neurons

Abstract

(−)-Epigallocatechin-3-gallate (EGCG), the main active component of green tea, is commonly known for its beneficial properties at low doses. On the other hand, little is known about the adverse effects of EGCG. Voltage-gated sodium channel (VGSC) is responsible for both initiation and propagation of action potentials of the neurons in the hippocampus and throughout the central nervous system (CNS). In this study, the effects of EGCG on voltage-gated sodium channel currents ( I Na) were investigated in rat primary cultures of hippocampal CA1 neurons via the conventional whole-cell patch-clamp technique. We found that I Na was not affected by EGCG at the concentration of 0.1 μM, but was completely blocked by EGCG at the concentration of 400 μM and higher, and EGCG reduced the amplitudes of I Na in a concentration-dependent manner in the range of 0.1–400 μM. Furthermore, our results also showed that at the concentration of 100 μM, EGCG was known to have the following performances: (1) it decreased the activation threshold and the voltage at which the maximum I Na current was evoked, caused negative shifts of I Na steady-state activation curve. (2) It enlarged I Na tail-currents. (3) It induced a left shift of the steady-state inactivation. (4) It reduced fraction of available sodium channels. (5) It delayed the activation of I Na in a voltage-dependent manner. (6) It prolonged the time course of the fast inactivation of sodium channels. (7) It accelerated the activity-dependent attenuation of I Na. On the basis of these findings, we propose that EGCG could impair certain physiological functions of VGSCs, which may contribute, directly or indirectly, to EGCG's effects in CNS.