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

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

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5748-5753
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number20
DOIs
StatePublished - May 17 2016
Externally publishedYes

Keywords

  • HERG safety assay
  • K channel screening
  • LFA
  • Liposome flux assay

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Novel cell-free high-throughput screening method for pharmacological tools targeting K<sup>+</sup> channels'. Together they form a unique fingerprint.

Cite this