Referenced in: none

Automatically associated channels: Kv11.1

Title: Novel cell-free high-throughput screening method for pharmacological tools targeting K+ channels.

Authors: Zhenwei Su, Emily C Brown, Weiwei Wang, Roderick MacKinnon

Journal, date & volume: Proc. Natl. Acad. Sci. U.S.A., 2016 May 17 , 113, 5748-53

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/27091997

Abstract
K(+) channels, a superfamily of ∼80 members, control cell excitability, ion homeostasis, and many forms of cell signaling. Their malfunctions cause numerous diseases including neuronal disorders, cardiac arrhythmia, diabetes, and asthma. Here we present a novel liposome flux assay (LFA) that is applicable to most K(+) channels. It is robust, low cost, and high throughput. Using LFA, we performed small molecule screens on three different K(+) channels and identified new activators and inhibitors for biological research on channel function and for medicinal development. We further engineered a hERG (human ether-à-go-go-related gene) channel, which, when used in LFA, provides a highly sensitive (zero false negatives on 50 hERG-sensitive drugs) and highly specific (zero false positives on 50 hERG-insensitive drugs), low-cost hERG safety assay.