I-Shan Chen, M. Tateyama, Y. Fukata
Sep 1, 2017
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1
Influential Citations
26
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Journal
The Journal of Physiology
Abstract
Ivermectin (IVM) is a widely used antiparasitic drug in humans and pets which activates glutamate‐gated Cl− channel in parasites. It is known that IVM binds to the transmembrane domains (TMs) of several ligand‐gated channels, such as Cys‐loop receptors and P2X receptors. We found that the G‐protein‐gated inwardly rectifying K+ (GIRK) channel, especially GIRK2, is activated by IVM directly in a Gβγ‐independent manner, but the activation is dependent on phosphatidylinositol‐4,5‐biphosphate (PIP2). We identified a critical amino acid residue of GIRK2 for activation by IVM, Ile82, located in the slide helix between the TM1 and the N‐terminal cytoplasmic tail domain (CTD). The results demonstrate that the TM–CTD interface in GIRK channel, rather than the TMs, governs IVM‐mediated activation and provide us with novel insights on the mode of action of IVM in ion channels.