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Effects of the calcium entry blocker bepridil on repolarizing and pacemaker currents in sheep cardiac Purkinje fibres

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Summary

(1) Effects of bepridil (0.3–100 μmol/l) on transmembrane currents which are active during the repolarization of the cardiac action potential were studied in sheep cardiac Purkinje fibres with the two-microelectrode voltage-clamp technique. Transmembrane currents were activated at a frequency of 0.03 Hz. (2) The initial inwardly rectifying current (i K1) was reduced by 1.8 μmol/l bepridil to 70% of the reference i K1-current in the absence of the drug. (3) An initial outward current, which is activated at positive membrane potentials (i inst) was depressed to 70% of reference by 14 μmol/l bepridil. (4) The time-dependent outward current (i K) was decreased by 1.8 μmol/l bepridil to 70% of its amplitude in the absence of bepridil. The biexponential time course of i K-current activation changed to be monoexponential with 100 μmol/l bepridil. The effect of bepridil on i K-current resulted in a shift of the activation curve of i K-current to more positive membrane potentials (10 μmol/l bepridil) and an additional decrease of driving force and/or conductance of the i K-channels with higher bepridil concentrations (100 μmol/l). (5) The transient outward current (i to) was completely blocked by 30 μmol/l bepridil. Inhibition to 70% of reference occurred with 1 μmol/l bepridil. The voltage-dependent inactivation of i to-current was affected by bepridil: the amplitude of the steady-state inactivation curve was reduced and i to-current was inactivated faster after application of bepridil. Bepridil caused no pronounced shift of the steady-state inactivation curve along the voltage axis. (6) The pacemaker current (i f) was slightly increased under the influence of low bepridil concentrations (0.3, 1 μmol/l) while it was reduced to 70% of reference by 100 μmol/l bepridil. (7) The blocking action of bepridil on outward currents in sheep cardiac Purkinje fibres will explain the action potential prolongation, which is observed in different mammalian cardiac tissues under the influence of bepridil.

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Authors and Affiliations

  1. Institut für Pharmakologie der Universität Düsseldorf, Moorenstrasse 5, D-4000, Düsseldorf, Federal Republic of Germany

    F. Berger, U. Borchard & D. Hafner

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  1. F. Berger
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  2. U. Borchard
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  3. D. Hafner
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Supported by the Deutsche Forschungsgemeinschaft SFB 242, C 1

Send offprint requests to U. Borchard at the above address

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Berger, F., Borchard, U. & Hafner, D. Effects of the calcium entry blocker bepridil on repolarizing and pacemaker currents in sheep cardiac Purkinje fibres. Naunyn-Schmiedeberg's Arch Pharmacol 339, 638–646 (1989). https://doi.org/10.1007/BF00168656

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