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

Hui Fang Li, Shih Ann Chen, Sheng-Nan Wu

Research output: Contribution to journalArticlepeer-review

119 Citations (Scopus)

Abstract

Objective: Resveratrol, a natural phytoalexin compound, is present in grapes and wine, and it can produce vasorelaxation. However, little is known of its mechanisms of action on ionic currents in endothelial cells. Methods: The effect of resveratrol on Ca2+-activated K+ currents in an endothelial cell line (HUV-EC-C) originally derived from human umbilical vein was investigated with the aid of the patch-clamp technique. Results: In the whole-cell configuration, resveratrol reversibly increased the amplitude of K+ outward currents. The increase in outward current caused by resveratrol was greatly inhibited by iberiotoxin (200 nM) or paxilline (1 μM), but not by glibenclamide (10 μM), tamoxifen (10 μM), or β-bungarotoxin (200 nM). Thus, this outward current is believed to be Ca2+-activated K+ current (I(K(Ca))). In the inside-out configuration, bath application of resveratrol (30 μM) caused no change in the single-channel conductance, but increased the activity of large-conductance Ca2+-activated K+ (BK(Ca)) channels. Resveratrol enhanced the channel activity in a concentration-dependent manner. The EC50 value for resveratrol-induced channel activity was 20 μM. The resveratrol-stimulated increase in the channel activity was independent of internal Ca2+. Resveratrol (30 μM) also shifted the activation curve of BK(Ca) channels to less positive membrane potentials. The change in the kinetic behavior of BK(Ca) channels caused by resveratrol in these cells is due to an increase in mean open time and a decrease in mean closed time. In a pancreatic islet endothelial cell line (MS1), resveratrol (30 μM) also increased the activity of intermediate-conductance K(Ca) channels. Conclusions: These results provide evidence that in addition to the presence of antioxidative activity, resveratrol can also stimulate K(Ca) channels in endothelial cells. The direct stimulation of these K(Ca) channels by resveratrol may be responsible for its effect on the functional activities of endothelial cells. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)1035-1045
Number of pages11
JournalCardiovascular Research
Volume45
Issue number4
DOIs
Publication statusPublished - 2000 Mar 1

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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