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The sulphonylurea glibenclamide inhibits voltage dependent potassium currents in human atrial and ventricular myocytes
Author(s) -
Schaffer Peter,
Pelzmann Brigitte,
Bernhart Eva,
Lang Petra,
Mächler Heinrich,
Rigler Bruno,
Koidl Bernd
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702904
Subject(s) - glibenclamide , depolarization , chemistry , medicine , potassium channel , cardiac transient outward potassium current , endocrinology , potassium channel blocker , inward rectifier potassium ion channel , myocyte , membrane potential , pharmacology , potassium , ic50 , electrophysiology , biophysics , patch clamp , in vitro , biochemistry , biology , ion channel , receptor , organic chemistry , diabetes mellitus
It was the aim of our study to investigate the effects of the sulphonylurea glibenclamide on voltage dependent potassium currents in human atrial myocytes. 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 μ M ) and was different from the ATP dependent potassium current I K(ATP) . 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 μ M . 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 μ M ). 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. In human ventricular myocytes glibenclamide inhibited I to1 without affecting the late current. Our data suggest that glibenclamide inhibits human voltage dependent cardiac potassium currents at concentrations above 10 μ M .British Journal of Pharmacology (1999) 128 , 1175–1180; doi: 10.1038/sj.bjp.0702904