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 sulphonylurea glibenclamide on voltage dependent potassium currents in human atrial myocytes. 2. The drug blocked a fraction of the quasi steady state current (ramp response) which was activated positive to −20 mV, was sensitive to 4-aminopyridine (500 μM) and was different from the ATP dependent potassium current I(K(ATP)). 3. Glibenclamide dose dependently inhibited both, the peak as well as the late current elicited by step depolarization positive to −20 mV. The IC(50) for reduction in charge area of total outward current was 76 μM. 4. The double-exponential inactivation time-course of the total outward current was accelerated in the presence of glibenclamide with a τ(fast) of 12.7±1.5 ms and a τ(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 μM). 5. Our data suggest, that both repolarizing currents in human atrial myocytes, the transient outward current (I(to1)) and the ultrarapid delayed rectifier current (I(Kur)) were inhibited by glibenclamide. 6. In human ventricular myocytes glibenclamide inhibited I(to1) without affecting the late current. 7. Our data suggest that glibenclamide inhibits human voltage dependent cardiac potassium currents at concentrations above 10 μM