Details

Autor(en) / Beteiligte

• Su, Zhenwei
• Brown, Emily C.
• Wang, Weiwei
• MacKinnon, Roderick

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2016-05, Vol.113 (20), p.5748-5753

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.