Swenson R P
J Gen Physiol. 1981 Mar;77(3):255-71. doi: 10.1085/jgp.77.3.255.
The characteristics of potassium channel block by a diverse group of quaternary ammonium (QA) ions was examined in squid axons. Altering the size and nature of the head and/or tail groups of the QA ions applied internally produced only quantitative differences in the potassium current block. Although their entry rate is diminished, compounds with head groups as large as 11 X 12 A are capable of occluding the channel, whereas the smallest QA ions, with head groups approximately 5 X 6 A, are not potent blockers. When one or three terminal hydrogens of the head group were replaced by hydroxyl moieties, the compound's blocking ability was diminished, suggesting that QA binding is not improved by hydrogen bonding at these positions. QA ions bound to their site within the potassium channel with 1:1 stoichiometry, and the site is perhaps 20% or more of the distance through the membrane electric field. Raising external potassium concentration did not alter the steady-state or kinetic features of the QA block of outward potassium currents; however, increasing temperature or adding Ba2+ internally increased the rate of decay of the QA-blocked currents. From the structure-function analysis of the QA ions, projections concerning both the architecture of the potassium channel's inner mouth and the significance of various chemical constituents of the ions were made. The potassium channel may now be pictured as having a wider mouth (up to 11 X 12 A) extending to the QA binding site and then narrowing quickly to the region of channel selectivity. Important alterations that improve the blocking ability of the compounds include: (a) lengthening the alkyl hydrocarbon tail group (up to 10 carbon), (b) lengthening a second hydrocarbon chain of the head group (e.g., decyldimethylphenylammonium bromide [C10DM phi]), and (c) adding a carbonyl moiety to the tail (e.g., ambutonium).
在枪乌贼轴突中研究了多种季铵（QA）离子对钾通道的阻断特性。在内部施加的QA离子的头部和/或尾部基团的大小和性质发生改变时，仅会在钾电流阻断方面产生定量差异。尽管它们的进入速率降低，但头部基团大至11×12 Å的化合物仍能够阻塞通道，而头部基团约为5×6 Å的最小QA离子则不是有效的阻断剂。当头部基团的一个或三个末端氢被羟基取代时，化合物的阻断能力会降低，这表明在这些位置通过氢键作用并不能改善QA的结合。QA离子以1:1的化学计量比结合到钾通道内的位点上，该位点可能在穿过膜电场距离的20%或更多。提高外部钾离子浓度不会改变外向钾电流的QA阻断的稳态或动力学特征；然而，升高温度或在内部添加Ba2+会增加QA阻断电流的衰减速率。通过对QA离子的结构-功能分析，对钾通道内口的结构以及离子的各种化学成分的重要性进行了推测。现在可以将钾通道描绘成具有一个较宽的口（最大为11×12 Å），延伸至QA结合位点，然后迅速变窄至通道选择性区域。能够提高化合物阻断能力的重要改变包括：（a）延长烷基烃尾部基团（最多10个碳），（b）延长头部基团的第二条烃链（例如，溴化癸基二甲基苯基铵 [C10DM phi]），以及（c）在尾部添加羰基部分（例如，安布铵）。
