Effects of the calcium entry blocker bepridil on repolarizing and pacemaker currents in sheep cardiac Purkinje fibres.
(1) Effects of bepridil (0.3-100 mumol/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 (iK1) was reduced by 1.8 mumol/l bepridil to 70% of the reference iK1-current in the absence of the drug. (3) An initial outward current, which is activated at positive membrane potentials (iinst) was depressed to 70% of reference by 14 mumol/l bepridil. (4) The time-dependent outward current (iK) was decreased by 1.8 mumol/l bepridil to 70% of its amplitude in the absence of bepridil. The biexponential time course of iK-current activation changed to be monoexponential with 100 mumol/l bepridil. The effect of bepridil on iK-current resulted in a shift of the activation curve of iK-current to more positive membrane potentials (10 mumol/l bepridil) and an additional decrease of driving force and/or conductance of the iK-channels with higher bepridil concentrations (100 mumol/l). (5) The transient outward current (ito) was completely blocked by 30 mumol/l bepridil. Inhibition to 70% of reference occurred with 1 mumol/l bepridil. The voltage-dependent inactivation of ito-current was affected by bepridil: the amplitude of the steady-state inactivation curve was reduced and ito-current was inactivated faster after application of bepridil. Bepridil caused no pronounced shift of the steady-state inactivation curve along the voltage axis.(ABSTRACT TRUNCATED AT 250 WORDS)
Berger
F
F
Institut für Pharmakologie der Universität Düsseldorf, Federal Republic of Germany.
Borchard
U
U
Hafner
D
D
D000818:Animals; D015764:Bepridil; D006321:Heart / Q000294:innervation; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D011690:Purkinje Fibers / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology*; D012756:Sheep
D007473:Ion Channels; D011759:Pyrrolidines; D015764:Bepridil