Jin W, Lu Z
Department of Physiology, University of Pennsylvania, Philadelphia 19104, USA.
Biochemistry. 1998 Sep 22;37(38):13291-9. doi: 10.1021/bi981178p.
Inward-rectifier K+ channels are a group of highly specialized K+ channels that accomplish a variety of important biological tasks. Inward-rectifier K+ channels differ from voltage-activated K+ channels not only functionally but also structurally. Each of the four subunits of the inward-rectifier K+ channels has only two instead of six transmembrane segments compared to the voltage-activated K+ channels. Thus far, there are no high-affinity ligands that directly target any inward-rectifier K+ channel. In the present study, we identified, purified, and synthesized a protein inhibitor of the inward-rectifier K+ channels. The inhibitor, called tertiapin, blocks a G-protein-gated channel (GIRK1/4) and the ROMK1 channel with nanomolar affinities, but a closely related channel, IRK1, is insensitive to tertiapin. Mutagenesis studies show that teritapin inhibits the channel by binding to the external end of the ion conduction pore.
内向整流钾通道是一组高度专业化的钾通道，它们完成各种重要的生物学任务。内向整流钾通道不仅在功能上，而且在结构上都与电压激活钾通道不同。与电压激活钾通道相比，内向整流钾通道的四个亚基中的每一个只有两个而不是六个跨膜片段。到目前为止，还没有直接靶向任何内向整流钾通道的高亲和力配体。在本研究中，我们鉴定、纯化并合成了一种内向整流钾通道的蛋白抑制剂。该抑制剂称为特律平，以纳摩尔亲和力阻断G蛋白门控通道（GIRK1/4）和ROMK1通道，但与之密切相关的通道IRK1对特律平不敏感。诱变研究表明，特律平通过与离子传导孔的外端结合来抑制通道。
