Tertiapin, a newly identified protein inhibitor, blocks G-protein-gated (GIRK1/4) and ROMK1 inward-rectifier K+ channels with nanomolar affinities by binding to the external end of the pore.
Tertiapin is identified as a high-affinity inhibitor of specific inward-rectifier K+ channels (GIRK1/4 and ROMK1), providing a novel tool for studying these channels.
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.
Jin et al. (Sat,) reported a other. tertiapin was evaluated on Inhibition of inward-rectifier K+ channels. Tertiapin, a newly identified protein inhibitor, blocks G-protein-gated (GIRK1/4) and ROMK1 inward-rectifier K+ channels with nanomolar affinities by binding to the external end of the pore.