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 microM) and was different from the ATP dependent potassium current IK(ATP). 3 Glibenclamide dose dependently inhibited both, the peak as well as the late current elicited by step depolarization positive to -20 mV. The IC50 for reduction in charge area of total outward current was 76 microM. 4 The double-exponential inactivation time-course of the total outward current 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 microM). 5 Our data suggest, that both repolarizing currents in human atrial myocytes, the transient outward current (Ito1) and the ultrarapid delayed rectifier current (IKur) were inhibited by glibenclamide. 6 In human ventricular myocytes glibenclamide inhibited Ito1 without affecting the late current. 7 Our data suggest that glibenclamide inhibits human voltage dependent cardiac potassium currents at concentrations above 10 microM.
Schaffer
P
P
Institut für Medizinische Physik und Biophysik, Karl-Franzens-Universität Graz, Harrachgasse 21, A-8010, Graz, Austria. Schaffer@balu.kfunigraz.ac.at
Pelzmann
B
B
Bernhart
E
E
Lang
P
P
Mächler
H
H
Rigler
B
B
Koidl
B
B
D000255:Adenosine Triphosphate / Q000502:physiology; D016275:Atrial Function; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005905:Glyburide / Q000494:pharmacology*; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects*; D013997:Time Factors; D016276:Ventricular Function
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D005905:Glyburide