Department of Pharmacology, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju 561-180, Korea.
Korean J Physiol Pharmacol. 2011 Oct;15(5):291-7. doi: 10.4196/kjpp.2011.15.5.291. Epub 2011 Oct 31.
The effect of cyclosporin A (CsA), an immunosuppressant, on human ether-a-go-go-related gene (HERG) channel as it is expressed in human embryonic kidney cells was studied using a whole-cell, patch-clamp technique. CsA inhibited the HERG channel in a concentration-dependent manner, with an IC(50) value and a Hill coefficient of 3.17 µM and 0.89, respectively. Pretreatment with cypermethrine, a calcineurin inhibitor, had no effect on the CsA-induced inhibition of the HERG channel. The CsA-induced inhibition of HERG channels was voltage-dependent, with a steep increase over the voltage range of the channel opening. However, the inhibition exhibited voltage independence over the voltage range of fully activated channels. CsA blocked the HERG channels predominantly in the open and inactivated states rather than in the closed state. Results of the present study suggest that CsA acts directly on the HERG channel as an open-channel blocker, and it acts independently of its effect on calcineurin activity.
采用全细胞膜片钳技术，研究了免疫抑制剂环孢素 A（CsA）对人胚肾细胞表达的人 ether-a-go-go 相关基因（HERG）通道的作用。CsA 呈浓度依赖性抑制 HERG 通道，IC（50）值和 Hill 系数分别为 3.17µM 和 0.89。钙调神经磷酸酶抑制剂氯菊酯预处理对 CsA 诱导的 HERG 通道抑制无影响。CsA 诱导的 HERG 通道抑制具有电压依赖性，在通道开放的电压范围内急剧增加。然而，在完全激活通道的电压范围内，抑制表现出电压独立性。CsA 主要在开放和失活状态而非关闭状态下阻断 HERG 通道。本研究结果表明，CsA 作为一种开放通道阻滞剂直接作用于 HERG 通道，其作用独立于对钙调神经磷酸酶活性的影响。
