Referenced in: none

Automatically associated channels: TRESK2

Title: Cloxyquin (5-chloroquinolin-8-ol) is an activator of the two-pore domain potassium channel TRESK.

Authors: Paul D Wright, Gregory Weir, Jamie Cartland, David Tickle, Catherine Kettleborough, M Zameel Cader, Jeff Jerman

Journal, date & volume: Biochem. Biophys. Res. Commun., 2013 Nov 15 , 441, 463-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24383077

Abstract
TRESK is a two-pore domain potassium channel. Loss of function mutations have been linked to typical migraine with aura and due to TRESK’s expression pattern and role in neuronal excitability it represents a promising therapeutic target. We developed a cell based assay using baculovirus transduced U20S cells to screen for activators of TRESK. Using a thallium flux system to measure TRESK channel activity we identified Cloxyquin as a novel activator. Cloxyquin was shown to have an EC50 of 3.8 μM in the thallium assay and displayed good selectivity against other potassium channels tested. Activity was confirmed using whole cell patch electrophysiology, with Cloxyquin causing a near two fold increase in outward current. The strategy presented here will be used to screen larger compound libraries with the aim of identifying novel chemical series which may be developed into new migraine prophylactics.