Glibenclamide inhibits agonist-induced Ca^2+ entry in cultured human aortic endothelial cells

It is well known that sulfonylureas, which block ATP-sensitive K^+ channels (K_ATP ), inhibit cystic fibrosis transmembrane regulator (CFTR) and volume-sensitive Cl^- channels in epithelial and cardiac cells. In this study, effects of glibenclamide on histamine-induced Cl^- current and Ca^2+ entry were investigated in fura-2 loaded cultured human endothelial cells. Glibenclamide inhibited the sustained [Ca^2+ ]_i increase induced by histamine in a concentration-dependent manner. The IC_50 value was 151.8 μM and the Hills coefficient was 1.9. Ca^2+ entry, induced by either 100 μM ATP or 10 μM cyclopiazonic acid, were also inhibited by glibenclamide. Membrane potentail was held at -50 mV by the voltage clamp, glibenclamide suppressed both histamine-induced Cl^- current and the sustained phase of the [Ca^2+ ]_i increase. Thus, the glibenclamide-induced inhibition of Ca^2+ entry was not due to possible changes of membrane potential followed by the suppression of Cl^- current. The present results indicate that glibenclamide disturbs the Ca^2+ influx pathway independently of the inhibition of Cl^- current. The activation of Cl^- channels might be functionally coupled with Ca^2+ influx pathway in vascular endothelial cells.