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

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.

SUBMITTER: Su Z

PROVIDER: S-EPMC4878532 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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

Su Zhenwei Z Brown Emily C EC Wang Weiwei W MacKinnon Roderick R

Proceedings of the National Academy of Sciences of the United States of America 20160418 20

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 ...[more]

PMID: 27091997

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