The catechin EGCG is the main flavonoid compound of green tea and has received enormous pharmacological attention because of its putative beneficial health effects. This study investigated for the first time the effect of EGCG on hERG channels, the main pharmacological target of drugs that cause acquired long QT syndrome. Cloned hERG channels were expressed in Xenopus oocytes and in HEK293 cells. Heterologous hERG currents were inhibited by EGCG with an IC50 of 6.0 mu mol/l in HEK293 cells and an IC50 of 20.5 mu mol/l in Xenopus laevis oocytes. Onset of effect was slow and only little recovery from inhibition was observed upon washout. In X. laevis oocytes EGCG inhibited hERG channels in the open and inactivated states, but not in the closed states. The half-maximal activation voltage of h ERG currents was shifted by EGCG towards more positive potentials. In conclusion, EGCG is a low-affinity inhibitor of hERG sharing major electrophysiological features with pharmaceutical hERG antagonists. (C) 2007 Elsevier Inc. All rights reserved.