Demo S D, Yellen G
Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, Maryland 21205.
Neuron. 1991 Nov;7(5):743-53. doi: 10.1016/0896-6273(91)90277-7.
Following voltage-dependent activation, Drosophila Shaker K+ channels enter a nonconducting, inactivated state. This process has been proposed to occur by a "ball-and-chain" mechanism, in which the N-terminus of the protein behaves like a blocker tethered to the cytoplasmic side of the channel and directly occludes the pore to cause inactivation. To complement the ample evidence for the involvement of the N-terminus, we sought evidence that it blocks the pore directly. We found that inactivation exhibits several distinctive properties of pore blockade. First, recovery was speeded by increased external K+ concentrations, just as blockade can be relieved by trans-permeant ions. Second, single-channel experiments show that the channel reopens from the inactivated state upon repolarization. These openings were usually required for recovery, as though the blocking particle must exit the pore before the channel can close.
在电压依赖性激活后，果蝇的Shaker钾离子通道进入非导电的失活状态。有人提出这个过程是通过“球链”机制发生的，在这种机制中，蛋白质的N端表现得像一个拴在通道细胞质侧的阻滞剂，直接阻塞孔道从而导致失活。为了补充大量关于N端参与的证据，我们寻找它直接阻塞孔道的证据。我们发现失活表现出孔道阻塞的几个独特特性。首先，外部钾离子浓度增加会加速恢复，就像阻滞剂可以被通透离子解除一样。其次，单通道实验表明，通道在复极化时从失活状态重新开放。这些开放通常是恢复所必需的，就好像阻塞颗粒必须在通道关闭之前离开孔道一样。
