Referenced in: none

Automatically associated channels: Kir1.1 , Kir2.1 , Kir3.1

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

Authors: W Jin, Z Lu

Journal, date & volume: Biochemistry, 1998 Sep 22 , 37, 13291-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/9748337

Abstract
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.