布比卡因的心脏毒性与HERG通道功能

人类HERG相关基因（humanether—a—go—go—relatedgene）编码的钾离子通道,是人类心肌重要的电压依赖性、快激活、延迟整流型钾离子通道,在心肌动作电位复极过程中起着至关重要的作用。多菲利特（dofetilide）、E-4031、和MK-499等药物能抑制延迟整流型钾电流,从而延长动作电位时程,其心电图主要表现为QT间期的延长。有实验研究显示微摩尔浓度的布比卡因即可阻断HERG通道,延长QT间期。而某些HERG通道激动剂具有增加该通道电流缩短QT间期的作用。本文从HERG通道的结构和功能、HERG激动剂作用机理、HERG通道与长QT综合征、布比卡因心脏毒性的关系等几个方面进行综述。

Bupivacaine cardiotoxicity and the function of HERG channel

The human ether-a-go-go-related gene （HERG） encoded delayed rectifier voltage gated K＋ channel （KCNH2, or Kvl 1.1） is a voltage-gated potassium channel mediated the IKr cur- rent. IKr is required for normal repolarization during the cardiac action potential. Dofetilide, E-4~31 and MK-499 can block the IKr current and increase action potential duration, which is detected on the surface electrocardiogram （ECG） as a prolongation of the QT interval. Micromolar concentra- tions of bupivacaine can inhibit the HERG channels and prolong QT interval. Some agonists of HERG channels can increase current and prolong QT interval. In this article, the structure and func- tion of HERG channels, the mechanism of HERG channels agonists, the relationship of HERG chan- nels and LQTS, and bupivacaine cardiac toxicity were reviewed.