- 作者: Ling-Ping Lai Ming-Jai Su Yung-Zu Tseng Wen-Pin Lien
- 作者服務機構: Institute of pharmacology, National tawian University and Department of Intermal medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC
- 中文摘要: --
- 英文摘要: The slow delayed rectifier potassium current(I ) isunique in its slow activation and deactivation kinetics. Itis important during cardiac repolarization, especiallywhen the heart rate is fast. We compared the effects ofquinidine, procainamide, sotalol, and amiodarone on I and correlated the findings with the clinical reverse use-dependent effects of potassium channel blockers. Hu-man minx RNA was obtained by reverse transcription-polymerase chain reaction using explanted humanheart. The RNA was injected into Xenopus oocytes forheterologous expression of I . A two-electrode voltageclamp technique was performed to investigate the I .We demonstrated that quinidine, sotalol and procainam-ide had no effects on I up to a concentration of 300μMwhile amiodarone inhibited I in a concentration-depen-dent manner starting from 10μM. The inhibition byamiodarone was state-dependent with gradual unblock-ing after depolarization. The degree of inhibition was53% immediately after depolarization and 19% at theend of a 5-second depolarization. I is 30 times moresensitive to amiodarone than to quinidine, sotalol, andprocainamide. Quinidine, sotalol and procainamide havereverse use-dependent effects while amiodarone doesnot. This is compatible with the hypothesis that no inhibi-tion of IKs at clinical concentrations contributes to theclinical reverse use-dependent effects.
- 中文關鍵字: --
- 英文關鍵字: Antiarrhythmic agents. Potssium channels. Votage clamp