A Thallium-Based Screening Procedure to Identify Molecules That Modulate the Activity of Ca2+-Activated Monovalent Cation-Selective Channels

SLAS Discov. 2018 Apr;23(4):341-352. doi: 10.1177/2472555217748932. Epub 2018 Jan 9.

Abstract

TRPM5 functions as a calcium-activated monovalent cation-selective ion channel and is expressed in a variety of cell types. Dysfunction of this type of channel has been recently implied in cardiac arrhythmias, diabetes, and other pathologies. Therefore, a growing interest has emerged to develop the pharmacology of these ion channels. We optimized a screening assay based on the thallium flux through the TRPM5 channel and a fluorescent thallium dye as a probe for channel activity. We show that this assay is capable of identifying molecules that inhibit or potentiate calcium-activated monovalent cation-selective ion channels.

Keywords: cell-based assays; fluorescence methods; high-content screening; ion channels; natural products screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism*
  • Cations, Monovalent
  • Cell Line
  • Fluorescent Dyes / metabolism
  • HEK293 Cells
  • High-Throughput Screening Assays / methods*
  • Humans
  • Ion Transport / drug effects*
  • TRPM Cation Channels / metabolism
  • Thallium / metabolism*

Substances

  • Cations, Monovalent
  • Fluorescent Dyes
  • TRPM Cation Channels
  • Thallium
  • Calcium