Barium-induced nondriven action potentials as a model of triggered potentials from early afterdepolarizations: significance of slow channel activity and differing effects of quinidine and amiodarone.
Triggered activity due to early afterdepolarizations in the context of prolonged repolarization is believed to cause torsade de pointes. The nature of such triggered activity is not clearly defined. Spontaneous action potentials developing from depolarized membrane potentials were studied in canine Purkinje fibers with use of a standard microelectrode technique. Action potentials due to abnormal automaticity and additional depolarizations developing over the repolarization phase were induced by 5 mM barium superfusion. These action potentials were abolished by 1.0 x 10(-5) M verapamil and by calcium-free solution, whereas action potential amplitude (Vmax) and spontaneous firing frequency were markedly enhanced by 2.0 x 10(-6) M isoproterenol. High calcium solution shortened the action potential duration and precluded additional depolarizations. Quinidine, 1.0 x 10(-5) M, reduced action potential amplitude (6.9 +/- 1.8%: p less than 0.01), Vmax (15.7 +/- 4.0%; p less than 0.05) and spontaneous firing frequency (18.5 +/- 2.1%; p less than 0.01), but it increased action potential duration measured at -40 mV (19.1 +/- 5.9%; p less than 0.01), which produced additional depolarizations. Amiodarone, 5.0 x 10(-5) M, reduced action potential amplitude (23.4 +/- 3.6%; p less than 0.01), Vmax (44.6 +/- 3.9%; p less than 0.01) and spontaneous firing frequency (41.9 +/- 5.1%; p less than 0.01). Amiodarone obviated the development of additional depolarizations without effect on action potential duration.(ABSTRACT TRUNCATED AT 250 WORDS)
Takanaka
C
C
Department of Medicine, University of California, Los Angeles.
Singh
B N
BN
D000200:Action Potentials / Q000187:drug effects; D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D001464:Barium / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D011690:Purkinje Fibers / Q000503:physiopathology*; D011802:Quinidine / Q000494:pharmacology*; D013610:Tachycardia / Q000139:chemically induced / Q000503:physiopathology*; D014700:Verapamil / Q000494:pharmacology
D015220:Calcium Channels; D001464:Barium; D014700:Verapamil; D011802:Quinidine; D007545:Isoproterenol; D000638:Amiodarone