Use-dependent blockers and exit rate of the last ion from the multi-ion pore of a K+ channel
Use-dependent blockers and exit rate of the last ion from the multi-ion pore of a K+ channel
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DOI：
10.1126/science.271.5249.653
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发表时间：
1996-02-02
期刊：
影响因子：
56.9
通讯作者：
Yellen, G
中科院分区：
文献类型：
--
作者：
Baukrowitz, T;Yellen, G
季铵阻滞剂从细胞内抑制许多电压激活的钾 (K+) 通道。当应用于哺乳动物细胞中表达的果蝇 Shaker 钾通道时，这些快速可逆的阻断剂通过一种不寻常的机制产生依赖于使用的抑制——它们促进了一种称为 C 型失活的内在构象变化，而这种变化的恢复很慢。阻滞剂通过切断钾离子流向孔中的某个位置来实现这一点，然后孔以每秒 10(5) 个离子的速度排空。这种缓慢的速率可能反映了最后一个离子从多离子孔中离开：由于离子-离子排斥，离子渗透（每秒 10(7)）很快发生，但最后离开的离子不会经历这种排斥。
Quaternary ammonium blockers inhibit many voltage-activated potassium (K+) channels from the intracellular side. When applied to Drosophila Shaker potassium channels expressed in mammalian cells, these rapidly reversible blockers produced use-dependent inhibition through an unusual mechanism-they promoted an intrinsic conformational change known as C-type inactivation, from which recovery is slow. The blockers did so by cutting off potassium ion flow to a site in the pore, which then emptied at a rate of 10(5) ions per second. This slow rate probably reflected the departure of the last ion from the multi-ion pore: Permeation of ions (at 10(7) per second) occurs rapidly because of ion-ion repulsion, but the last ion to leave would experience no such repulsion.