Effects Of EGCG On The Voltage-gated Potassium Channels In Primary Cultured Hippocampal Cells

It is reported that Epigallocatechin-3-gallate (EGCG), one of the major tea catechins, has various beneficial effects, including antioxidant, anti-inflammation, anti-obesity, anti-cancer and so on. But recently studies in cultured hippocampal cells and brain slice found that high dose EGCG exerted certain kinds of side effects, which may relate to the voltage-gated channel. In order to further study the possible side effects caused by high dose EGCG in the central neural system, we investigate the effects of high dose EGCG on the voltage-gated potassium channels especially on transient outward potassium current and delayed rectifier potassium current in primary cultured hippocampal neurons.Using whole-cell clamp patch, we studied the possible influence of EGCG on the current-voltage, activation and inactivation of I_A and I_K. Our results indicated that :(1) EGCG did inhibit the current amplitude of both I_A and I_K, besides, this inhibition was in a dose-dependent manner. The half maximum concentration of I_A and I_K are 251.70±37.47μM,181.8±9.33μM, respectively.(2) The inhibition of 200μM EGCG on I_A and I_K were in a voltage-dependent manner, and this inhibition increased with the depolarization of voltage.(3) The activation curves of both I_A and I_K were shifted to the hyperpolarization direction by EGCG, which means the channels can be activated at a more negative voltage. And the half activated voltages were shifted by 11.7mV and 6.4mV, correspondingly.(4) EGCG can shift the inactivation curves of both I_A and I_K to the hyperpolarization, in this case, the channels can be inactivated at a more negative voltage. This will leads to the decrease of the currents in both I_A and I_K. And the half inactivation curves for I_A and I_K were shifted by 20.72mV and 14.86mV, respectively. Generally, the move of the inactivation curve to the left means there are less channels which can be activated under a certain voltage. This may be the direct reason for the decrease of current amplitude caused by EGCG.(5) Compare the shifts caused by EGCG of activation curves and inactivation curves, we found that the inactivation curves in both I_A and I_K were shifted to a more negative than that of activation curves. (6) We compare the effects of I_A and I_K elicited by EGCG, the changes of activation and inactivation of I_A were bigger than that of I_K. The Hill coefficient may help explain this phenomenon, but we are uncertain about that.In the central nervous system, the voltage-gated potassium channel currents play important roles in maintaining of the excitability and the recovery of action potential in neurons. The dysfunction of these channels will result in the abnormal of firing pattern and discharge. Our study showed that high dose EGCG can alter the dynamics of I_A and I_K, including the current-voltage, activation and inactivation properties. This reminds us to be careful when use the EGCG as possible therapy against obesity, cancer, inflammation and so on, the improper use of EGCG may cause serious damage to certain population.