Effects of (−)-epigallocatechin-3-gallate in Ca2+-permeable non-selective cation channels and voltage-operated Ca2+ channels in vascular smooth muscle cells

The effects of (−)-epigallocatechin-3-gallate (EGCG), the most abundant catechin of tea, on Ca2+-permeable non-selective cation currents (NSCC) and voltage-operated Ca2+ channels (VOCC) have been investigated in cultured rat aortic smooth muscle cells using the whole-cell voltage-clamp technique. Under the Cs+/tetraethylammonium (TEA)-containing internal solution, and in the presence of nifedipine (1 μM), EGCG (30 μM) activated a long-lasting inward current, with a reversal potential (Erev) of approximately 0 mV. This current was not significantly altered by the replacement of [Cl−]i or [Cl−]o, implying that the inward current was not a chloride channel, but a NSCC. SKF 96365 (30 μM) and Cd2+ (500 μM) almost completely abolished the EGCG-induced NSCC. A higher dose of EGCG (100 μM) additionally activated a nifedipine-sensitive inward current in the absence of depolarization protocol. EGCG (100 μM) also potentiated a nifedipine-sensitive voltage-dependent Ba2+-current during the first 5 min of incubation. However, after > 10 min of incubation with EGCG, this current was significantly inhibited. Our results suggest that EGCG caused a Ca2+ influx into smooth muscle cells via VOCC (probably L-type) and other SKF-96365- and Cd2+-sensitive Ca2+-permeable channels. The action described here may be responsible for the contraction induced by EGCG in rat aortic rings and for the rise of the intracellular concentration of Ca2+ in rat aortic smooth muscle cells evoked by this catechin. On the other hand, the inhibition of VOCC after > 10 min of incubation may be, in part, responsible for the relaxation of rat aorta induced by EGCG.