Termination of Aconitine-Induced Atrial Fibrillation by the KAch-Channel Blocker Tertiapin: Underlying Electrophysiological Mechanism

The acetylcholine receptor-operated K+ (K-Ach) channel may be a novel target for atrial-specific antiarrhythmic therapy. Recently it has been demonstrated that tertiapin, a selective blocker of K-Ach channel, suppressed aconitine-induced atrial fibrillation (AF) in dogs. However, the precise mechanism by which the K-Ach-channel blocker inhibits the aconitine-induced AF remains unknown. This study was undertaken to determine the role of K-Ach channel in aconitine-induced AF in guinea pigs. Tertiapin terminated the aconitine-induced AF in anesthetized guinea pigs. The results of an in vitro electrophysiological experiment using atrial cells and atrial preparations suggest that aconitine might activate K-Ach channels in atrial cells, probably by intracellular Na+ accumulation, and inhibition of K-Ach channels by tertiapin might suppress AF by producing conduction block, probably due to further decrease in the resting membrane potential. Since it has been reported that constitutively active K-Ach channels can be observed in atrial cells of patients with chronic AF, aconitine-induced AF may be used as an experimental model for evaluation of drug effect on chronic AF.