title: Termination of aconitine-induced atrial fibrillation by the KACh-channel blocker tertiapin: underlying electrophysiological mechanism.
abstract: The acetylcholine receptor-operated K(+) (KACh) channel may be a novel target for atrial-specific antiarrhythmic therapy. Recently it has been demonstrated that tertiapin, a selective blocker of KACh channel, suppressed aconitine-induced atrial fibrillation (AF) in dogs. However, the precise mechanism by which the KACh-channel blocker inhibits the aconitine-induced AF remains unknown. This study was undertaken to determine the role of KACh 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 KACh channels in atrial cells, probably by intracellular Na(+) accumulation, and inhibition of KACh 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 KACh 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.
authors.affiliation: Department of Pharmacology, Chiba University Graduate School of Medicine, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Suzuki
authors.forename: Akio
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nishida
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Reien
authors.forename: Hiroo
authors.initials: H
authors.lastname: Maruyama
authors.forename: Haruaki
authors.initials: H
authors.lastname: Nakaya
mesh_terms: D000157:Aconitine / Q000009:adverse effects*; D000818:Animals; D001281:Atrial Fibrillation / Q000139:chemically induced* / Q000188:drug therapy*; D001514:Bee Venoms / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D002908:Chronic Disease; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D055724:Electrophysiological Phenomena / Q000187:drug effects; D006168:Guinea Pigs; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D058990:Molecular Targeted Therapy; D026902:Potassium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology; D012964:Sodium / Q000378:metabolism
chemical_list: D001514:Bee Venoms; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C029738:tertiapin; D012964:Sodium; D000157:Aconitine