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  • 标题:Effects of Oxypeucedanin on hKv1.5 and Action Potential Duration
  • 本地全文:下载
  • 作者:Jae Soon Eun ; Jung Ah Park ; Bok Hee Choi
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:2005
  • 卷号:28
  • 期号:4
  • 页码:657-660
  • DOI:10.1248/bpb.28.657
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:A furocoumarin derivative, oxypeucedanin, was purified from Angelica dahurica , and its effects on the human Kv1.5 (hKv1.5) channel and on the cardiac action potential duration (APD), were examined using the patch-clamp technique and the conventional microelectrode technique. Oxypeucedanin inhibited the hKv1.5 current in a concentration-dependent manner, with an IC50 value of 76 n M , while it had no effect on human eag-related gene (HERG) current. Oxypeucedanin induced an initial fast decline of hKv1.5 current during depolarizations. The inhibition of hKv1.5 channel by oxypeucedanin was voltage-dependent, especially at depolarizing pulses between −40 and 0 mV which corresponds to the voltage range of the channel's opening. Oxypeucedanin also slowed the deactivation time course, resulting in a tail crossover phenomenon. Additionally, oxypeucedanin prolonged the APD of rat atrial and ventricular muscles in a dose-dependent manner. These results suggest that oxypeucedanin is a kind of open-channel blocker of the hKv1.5 channel and it prolongs the APD; therefore, it is an excellent candidate as an antiarrhythmic drug for atrial fibrillation.
  • 关键词:hKv1.5 channel blocker;antiarrhythmic drug;oxypeucedanin;Angelica dahurica
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