Effects of the potassium channel activator, BRL 34915, on the action potential characteristics of canine cardiac Purkinje fibers.
The effects of various concentrations (1-100 microM) of BRL 34915 on the action potential characteristics were investigated in normal canine Purkinje fibers and Purkinje fibers surviving infarction. For comparison, the electrophysiological effects of BRL 34915 were also examined in normal Purkinje fibers in which the potassium conductance had been reduced by barium. In normal Purkinje fibers, BRL 34915 produced a concentration-dependent shortening of action potential duration (APD) without change in the maximum diastolic potential, action potential amplitude or maximum upstroke velocity. A similar shortening of APD was observed in Purkinje fibers surviving infarction and in barium-treated Purkinje fibers. The reduction of APD by BRL 34915 was more pronounced at a longer cycle length of stimulation than at a shorter cycle length. In normal Purkinje fibers and in Purkinje fibers surviving infarction, depolarizations produced by low external potassium (1 mM) were attenuated by the drug, whereas there were little or no effects on high potassium (4-8 mM)-induced depolarization. Barium-treated Purkinje fibers when depolarized by 1 mM potassium were not sensitive to the hyperpolarizing effect of BRL 34915. It is proposed that the unique electrophysiological activity of BRL 34915 in canine Purkinje fibers is related to an increase in the potassium currents, ix1, ik1, and the ATP-sensitive potassium current in these fibers.
Bril
A
A
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Man
R Y
RY
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001464:Barium / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D004285:Dogs; D004594:Electrophysiology; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects*; D011690:Purkinje Fibers / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*
D000959:Antihypertensive Agents; D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D001464:Barium