Modulation of ERG channels by XE991.

Research output: Contribution to journalJournal articleResearchpeer-review

In neuronal tissue, KCNQ2-5 channels conduct the physiologically important M-current. In some neurones, the M-current may in addition be conducted partly by ERG potassium channels, which have widely overlapping expression with the KCNQ channel subunits. XE991 and linopiridine are known to be standard KCNQ potassium channel blockers. These compounds have been used in many different tissues as specific pharmacological tools to discern native currents conducted by KCNQ channels from other potassium currents. In this article, we demonstrate that ERG1-2 channels are also reversibly inhibited by XE991 in the micromolar range (EC(50) 107 microM for ERG1). The effect has been characterized in Xenopus laevis oocytes expressing ERG1-2 and in the mammalian HEK293 cell line stably expressing ERG1 channels. The IC(50) values for block of KCNQ channels by XE991 range 1-65 microM. In conclusion, great care should be taken when choosing the concentration of XE991 to use for experiments on native potassium channels or animal studies in order to be able to conclude on selective KCNQ channel-mediated effects.
Original languageEnglish
JournalBasic & Clinical Pharmacology & Toxicology
Issue number5
Pages (from-to)316-22
Number of pages6
Publication statusPublished - 2007

Bibliographical note

Keywords: Acetylcholine; Animals; Anthracenes; Carbamates; Cell Line; Chromans; Dose-Response Relationship, Drug; Electrophysiology; Ether-A-Go-Go Potassium Channels; Gene Expression; Indoles; Oocytes; Patch-Clamp Techniques; Phenylenediamines; Potassium Channel Blockers; Potassium Channels, Voltage-Gated; Pyridines; Xenopus laevis

ID: 8418570