Circulation, Vol 82, 289-293, Copyright © 1990 by American Heart Association
CH Follmer and TJ Colatsky
Block of the delayed rectifier potassium current, IK, by the class IC
antiarrhythmic agent, flecainide, and by the novel selective class III
antiarrhythmic agent, E-4031, were compared in isolated cat ventricular
myocytes using the single suction-pipette, voltage-clamp technique.
Flecainide (10 microM) markedly reduced IK elicited on depolarization steps
to plateau voltages (+10 mV) and nearly completely blocked the "tail
currents" elicited on repolarization to -40 mV (93 +/- 4% block at +40 mV,
n = 3). E-4031 (1 microM) produced similar effects (96 +/- 3% block at +40
mV, n = 3). Slow voltage ramps from -100 to +40 mV confirmed inward
rectifying properties of IK and showed that flecainide and E-4031 have no
effects on the background potassium current, IK1. Thus, the results
demonstrate that block of IK is a common feature of flecainide and E-4031.
IK block by E-4031 most likely underlies the drug's potent class III
antiarrhythmic properties. On the other hand, flecainide block of IK during
an action potential would tend to prolong repolarization, but this effect
may be obscured by concomitant block of plateau Na+ channels to produce
little or no change in action potential duration, consistent with its class
IC classification.
ARTICLES
Block of delayed rectifier potassium current, IK, by flecainide and E- 4031 in cat ventricular myocytes
Cardiovascular Pharmacology, Wyeth-Ayerst Research, Princeton, NJ 08543- 8000.
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