The sulphonylurea glibenclamide inhibits voltage dependent potassium currents in human atrial and ventricular myocytes

1 It was the aim of our study to investigate the effects of the sulphonylur ea glibenclamide on voltage dependent potassium currents in human atrial my ocytes. 2 The drug blocked a fraction of the quasi steady state current (ramp respo nse) which was activated positive to -20 mV, was sensitive to 4-aminopyridi ne (500 mu M) and was different from the ATP dependent potassium current I- K(ATP) 3 Glibenclamide dose dependently inhibited both, the peak as well as the la te current elicited by step depolarization positive to -20 mV. The IC50 for reduction in charge area of total outward current was 76 mu M. 4 The double-exponential inactivation time-course of the total outward curr ent was accelerated in the presence of glibenclamide with a tau(fast) of 12 .7+/-1.5 ms and a tau(slow) of 213+/-25 ms in control and 5.8+/-1.9 ms (P<0 .001) and 101+/-20 ms (P<0.05) under glibenclamide (100 mu M). 5 Our data suggest, that both repolarizing currents in human atrial myocyte s, the transient outward current (I-to1) and the ultrarapid delayed rectifi er current (I-Kur) were inhibited by glibenclamide. 6 In human ventricular myocytes glibenclamide inhibited I-to1 without affec ting the late current. 7 Our data suggest that glibenclamide inhibits human voltage dependent card iac potassium currents at concentrations above 10 mu M.