Evidence for the stimulatory effect of resveratrol on Ca2+-activated K+ current in vascular endothelial cells

Objective: Resveratrol, a natural phytoalexin compound, is present in grape s and wine, and it can produce vasorelaxation. However, little is known of its mechanisms of action on ionic currents in endothelial cells. Methods: T he effect of resveratrol on Ca2+-activated K+ currents in an endothelial ce ll line (HUV-EC-C) originally derived from human umbilical vein was investi gated with the aid of the patch-clamp technique. Results: In the whole-cell configuration, resveratrol reversibly increased the amplitude of K+ outwar d currents. The increase in outward current caused by resveratrol was great ly inhibited by iberiotoxin (200 nM) or paxilline (1 mu M), but not by glib enclamide (10 mu M), tamoxifen (10 mu M), or beta-bungarotoxin (200 nM). Th us, this outward current is believed to be Ca2+-activated K+ current (I-K(C a)). In the inside-out configuration, bath application of resveratrol (30 m u M) caused no change in the single-channel conductance, but increased the activity of large-conductance Ca2+-activated K+ (BKCa) channels. Resveratro l enhanced the channel activity in a concentration-dependent manner. The EC 50 value for resveratrol-induced channel activity was 20 mu M. The resverat rol-stimulated increase in the channel activity was independent of internal Ca2+. Resveratrol (30 mu M) also shifted the activation curve of BKCa chan nels to less positive membrane potentials. The change in the kinetic behavi or of BKCa channels caused by resveratrol in these cells is due to an incre ase in mean open time and a decrease in mean closed time. In a pancreatic i slet endothelial cell line (MS1), resveratrol (30 mu M) also increased the activity of intermediate-conductance K-Ca channels. Conclusions: These resu lts provide evidence that in addition to the presence of antioxidative acti vity, resveratrol can also stimulate K-Ca channels in endothelial cells. Th e direct stimulation of these K-Ca channels by resveratrol may be responsib le for its effect on the functional activities of endothelial cells. (C) 20 00 Elsevier Science BN. All rights reserved.