Identifying regulators for EAG1 channels with a novel electrophysiology and tryptophan fluorescence based screen.

• Main Authors: Tinatin I Brelidze, Anne E Carlson, Douglas R Davies, Lance J Stewart, William N Zagotta
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2010-09-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC2932742?pdf=render

Ether-à-go-go (EAG) channels are expressed throughout the central nervous system and are also crucial regulators of cell cycle and tumor progression. The large intracellular amino- and carboxy- terminal domains of EAG1 each share similarity with known ligand binding motifs in other proteins, yet EAG1 channels have no known regulatory ligands.Here we screened a library of small biologically relevant molecules against EAG1 channels with a novel two-pronged screen to identify channel regulators. In one arm of the screen we used electrophysiology to assess the functional effects of the library compounds on full-length EAG1 channels. In an orthogonal arm, we used tryptophan fluorescence to screen for binding of the library compounds to the isolated C-terminal region.Several compounds from the flavonoid, indole and benzofuran chemical families emerged as binding partners and/or regulators of EAG1 channels. The two-prong screen can aid ligand and drug discovery for ligand-binding domains of other ion channels.