Inhibition of the cloned delayed rectifier K+ channels, Kv1.5 and Kv3.1, by riluzole
Inhibition of the cloned delayed rectifier K+ channels, Kv1.5 and Kv3.1, by riluzole
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DOI：
10.1016/j.neuroscience.2005.03.041
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发表时间：
2005-01-01
期刊：
影响因子：
3.3
通讯作者：
Hahn, SJ
中科院分区：
文献类型：
--
作者：
Ahn, HS;Choi, JS;Hahn, SJ
使用全细胞膜片钳技术检查了神经保护药物利鲁唑对克隆的延迟整流 K 通道（Kv1.5 和 Kv3.1）的作用。利鲁唑以浓度依赖性方式可逆地抑制 Kv1.5 电流，IC50 为 39.69 +/- 2.37 mu M。G 蛋白抑制剂（百日咳毒素和 GDP beta S）不能阻止利鲁唑对 Kv1.5 的抑制。在通道完全激活的电压范围内，没有发现利鲁唑具有电压依赖性抑制作用。利鲁唑以浓度依赖性方式使 Kv1.5 的稳态失活曲线向超极化方向移动。它以浓度依赖性方式加速 Kv1.5 的失活动力学，但对稳态激活曲线没有影响。利鲁唑表现出对 Kv1.5 的非使用依赖性抑制。还检查了利鲁唑对 Kv3.1（Shaw 型 K 通道）的影响。 Riluzole 对 Kv3.1 电流产生浓度依赖性抑制，IC50 为 120.98 +/- 9.74 μM，并且还使 Kv3.1 的稳态失活曲线向超极化方向移动。因此，利鲁唑以浓度依赖性方式抑制 Kv1.5 和 Kv3.1 电流，并通过优先与通道的失活和关闭状态结合而直接与 Kv1.5 相互作用。 (c) 2005 年由 Elsevier Ltd 代表 IBRO 出版。
The action of riluzole, a neuroprotective drug, on cloned delayed rectifier K channels (Kv1.5 and Kv3.1) was examined using the whole-cell patch-clamp technique. Riluzole reversibly inhibited Kv1.5 currents in a concentration-dependent manner with an IC50 of 39.69 +/- 2.37 mu M. G-protein inhibitors (pertussis toxin and GDP beta S) did not prevent this inhibition of riluzole on Kv1.5. No voltage-dependent inhibition by riluzole was found over the voltage range in which channels are fully activated. Riluzole shifted the steady-state inactivation curves of Kv1.5 in a hyperpolarizing direction in a concentration-dependent manner. It accelerated the deactivation kinetics of Kv1.5 in a concentration dependent-manner, but had no effect on the steady-state activation curve. Riluzole exhibited a use-independent inhibition of Kv1.5. The effects of riluzole on Kv3.1, the Shaw-type K channel were also examined. Riluzole caused a concentration-dependent inhibition of Kv3.1 currents with an IC50 of 120.98 +/- 9.74 mu M and also shifted the steady-state inactivation curve of Kv3.1 in the hyperpolarizing direction. Thus, riluzole inhibits both Kv1.5 and Kv3.1 currents in a concentration-dependent manner and interacts directly with Kv1.5 by preferentially binding to the inactivated and to the closed states of the channel. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.