A novel high-affinity inhibitor for inward-rectifier K+ channels

被引：189

作者：

Jin, WL ^{[1
]}

Lu, Z ^{[1
]}

机构：

[1] Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA

来源：

BIOCHEMISTRY | 1998年 / 37卷 / 38期

关键词：

D O I：

10.1021/bi981178p

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

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页码：13291 / 13299

页数：9

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