Flecainide inhibits the transient outward current in atrial myocytes isolated from the rabbit heart.
We examined the effects of flecainide, a class Ic antiarrhythmic agent, on membrane currents in single rabbit atrial myocytes, using the tight-seal whole cell voltage-clamp technique. Under the current-clamp condition, flecainide (1-100 microM) prolonged the action potential duration at both the early and the late phases of repolarization in a concentration-dependent manner without affecting the resting membrane potential. In the presence of 4-aminopyridine, however, the drug affected the atrial action potential duration differently than it did in the absence of 4-aminopyridine: it shortened the early phase and only slightly lengthened the late phase of the atrial action potential. Under the voltage-clamp condition, flecainide suppressed the 4-amino-pyridine-sensitive, Ca(++)-insensitive transient outward current in a concentration-dependent fashion (the concentration for the half-maximal effect was approximately 17 microM). The drug also slightly inhibited the voltage-dependent L-type Ca++ current and delayed outward K+ current. Flecainide apparently accelerated the inactivation time course of the transient outward current but did not affect the voltage-dependence of its steady-state inactivation. These actions of flecainide on the transient outward current could be described by a voltage-dependent first-order interaction of the drug with the channel.
Yamashita
T
T
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Nakajima
T
T
Hamada
E
E
Hazama
H
H
Omata
M
M
Kurachi
Y
Y
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D016275:Atrial Function; D005424:Flecainide / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects*; D066298:In Vitro Techniques; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D011817:Rabbits
D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D015761:4-Aminopyridine; D005424:Flecainide