Baukrowitz T, Yellen G
Department of Neurobiology, Massachusetts General Hospital, Boston 02114, USA.
Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13357-61. doi: 10.1073/pnas.93.23.13357.
Many blockers of Na+ and K+ channels act by blocking the pore from the intracellular side. For Shaker K+ channels, such intracellular blockers vary in their functional effect on slow (C-type) inactivation: Some blockers interfere with C-type inactivation, whereas others do not. These functional differences can be explained by supposing that there are two overlapping "subsites" for blocker binding, only one of which inhibits C-type inactivation through an allosteric effect. We find that the ability to bind to these subsites depends on specific structural characteristics of the blockers, and correlates with the effect of mutations in two distinct regions of the channel protein. These interactions are important because they affect the ability of blockers to produce use-dependent inhibition.
许多钠通道和钾通道阻滞剂通过从细胞内侧阻断孔道来发挥作用。对于摇椅式钾通道，此类细胞内阻滞剂对缓慢（C型）失活的功能影响各不相同：一些阻滞剂会干扰C型失活，而另一些则不会。这些功能差异可以通过假设存在两个重叠的阻滞剂结合“亚位点”来解释，其中只有一个通过变构效应抑制C型失活。我们发现，与这些亚位点结合的能力取决于阻滞剂的特定结构特征，并与通道蛋白两个不同区域的突变效应相关。这些相互作用很重要，因为它们会影响阻滞剂产生使用依赖性抑制的能力。
