Baukrowitz T, Yellen G
Department of Neurobiology, Harvard Medical School and Massachusetts General Hospital, Boston 02114, USA.
Science. 1996 Feb 2;271(5249):653-6. doi: 10.1126/science.271.5249.653.
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.
季铵类阻滞剂可从细胞内侧抑制多种电压激活钾（K+）通道。当将其应用于在哺乳动物细胞中表达的果蝇Shaker钾通道时，这些快速可逆的阻滞剂通过一种不同寻常的机制产生了使用依赖性抑制作用——它们促使一种被称为C型失活的内在构象变化，从这种变化中恢复很慢。阻滞剂通过切断钾离子向孔中一个位点的流动来实现这一点，然后该位点以每秒10⁵个离子的速率排空。这个缓慢的速率可能反映了最后一个离子从多离子孔中离开：由于离子间的排斥作用，离子的通透（每秒10⁷个）很快发生，但最后一个离开的离子不会经历这种排斥作用。
