Busch A E, Herzer T, Takumi T, Krippeit-Drews P, Waldegger S, Lang F
Physiologisches Institut I, Eberhard-Karls-Universität Tübingen, Germany.
Eur J Pharmacol. 1994 Oct 13;264(1):33-7. doi: 10.1016/0014-2999(94)90632-7.
cRNA encoding the human IsK protein was injected into Xenopus oocytes and the expressed channels were investigated using the two-microelectrode voltage-clamp method. The novel class III antiarrhythmic NE-10064 (1-[[[5-(4-chlorophenyl)-2-furanyl]methylene]-amino]-3- [4-(4-methyl-1-piperazinyl)-butyl]-2,4-imidazolidinedione dihydrochloride) was tested for its ability to block these channels. The compound displayed potent inhibitory effects with an EC50 of 5.4 microM. The block caused by NE-10064 was use-dependent, i.e. channels had to be activated for the inhibition to occur. Further, the reversal of the inhibition during the wash-out period was use-dependent. Finally, the blockade of human IsK channels by NE-10064 appeared to be voltage-dependent, being more pronounced at depolarized potentials. We conclude that this novel class III antiarrhythmic is a potent inhibitor of human IsK channels and suggest that such effects could be involved in its antiarrhythmic action.
将编码人IsK蛋白的cRNA注入非洲爪蟾卵母细胞，并使用双微电极电压钳法研究表达的通道。对新型III类抗心律失常药物NE - 10064（1 - [[[5 - （4 - 氯苯基） - 2 - 呋喃基]亚甲基] - 氨基] - 3 - [4 - （4 - 甲基 - 1 - 哌嗪基） - 丁基] - 2,4 - 咪唑烷二酮二盐酸盐）阻断这些通道的能力进行了测试。该化合物表现出强效抑制作用，EC50为5.4微摩尔。NE - 10064引起的阻断具有使用依赖性，即通道必须被激活才能发生抑制作用。此外，洗脱期内抑制作用的逆转也具有使用依赖性。最后，NE - 10064对人IsK通道的阻断似乎具有电压依赖性，在去极化电位时更为明显。我们得出结论，这种新型III类抗心律失常药物是人类IsK通道的强效抑制剂，并表明这种作用可能与其抗心律失常作用有关。
