Effects of calcium channel blockers on cloned cardiac K+ channels IKr and IKs.
Effects of calcium channel blockers on cloned cardiac K+ channels IKr and IKs.
复制标题
钙通道阻滞剂对克隆心脏 K 通道 IKr 和 IK 的影响。
DOI：
--
复制
发表时间：
2000
期刊：
影响因子：
--
通讯作者：
J. Barhanin
中科院分区：
文献类型：
--
作者：
C. Chouabe;M. Drici;G. Romey;J. Barhanin
克隆的HERG和KvLQT 1-IsK K+通道已在哺乳动物细胞中表达，并作为钙通道阻滞剂的靶点进行测定。这些通道产生心脏延迟整流K+电流的快速和缓慢成分，突变可以影响它们，导致长QT综合征。HERG被苄普地尔（EC 50 = 0.55 μ M）、维拉帕米（EC 50 = 0.83 μ M）和米贝拉地尔（EC 50 = 1.43 μ M）阻断，而尼群地平和地尔硫卓的作用可以忽略不计。在阻断剂存在下，稳态激活和失活参数变为更负的值。类似地，KvLQT 1-IsK被苄普地尔（EC 50 = 10.0 μ M）和米贝拉地尔（EC 50 = 11.8 μ M）抑制，而对尼群地平、地尔硫卓或维拉帕米不敏感。这项工作可能有助于了解维拉帕米在某些室性心动过速以及与苄普地尔和米贝拉地尔相关的一些有害不良心脏事件中的作用机制。
Cloned HERG and KvLQT1-IsK K+ channels have been expressed in mammalian cells and assayed as a target for calcium channel blockers. These channels generate the rapid and slow components of the cardiac delayed rectifier K+ current, and mutations can affect them that lead to long QT syndromes. HERG is blocked by bepridil (EC50 = 0.55 microM), verapamil (EC50 = 0.83 microM) and mibefradil (EC50 = 1.43 microM), whereas nitrendipine and diltiazem have negligible effects. Steady-state activation and inactivation parameters are shifted to more negative values in the presence of the blockers. Similarly, KvLQT1-IsK is inhibited by bepridil (EC50 = 10.0 microM) and mibefradil (EC50 = 11.8 microM), whilst being insensitive to nitrendipine, diltiazem or verapamil. This work may help to understand the mechanisms of action of verapamil in certain ventricular tachycardias as well as some of the deleterious adverse cardiac events associated with bepridil and mibefradil.