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Modulation of ERG Channels by XE991
Author(s) -
Elmedyb Pernille,
Calloe Kirstine,
Schmitt Nicole,
Hansen Rie Schultz,
Grunnet Morten,
Olesen SørenPeter
Publication year - 2007
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2007.00048.x
Subject(s) - potassium channel , xenopus , chemistry , potassium channel blocker , biophysics , potassium , pharmacology , microbiology and biotechnology , biology , biochemistry , gene , organic chemistry
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 µM 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 µM. 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.