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Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Modulation of ERG channels by XE991.
Pernille Elmedyb1, Kirstine Calloe, Nicole Schmitt
1Department of Medical Physiology, The Panum Institute, The University of Copenhagen, Denmark.
Basic & Clinical Pharmacology & Toxicology
|April 24, 2007
Summary
The KCNQ channel blocker XE991 also inhibits ERG potassium channels at higher concentrations. Researchers must carefully select XE991 concentrations to ensure selective KCNQ channel studies.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- KCNQ2-5 channels conduct the M-current in neurons.
- ERG potassium channels may also contribute to the M-current.
- XE991 is a known KCNQ channel blocker used in research.
Purpose of the Study:
- To investigate the specificity of XE991 as a KCNQ channel blocker.
- To determine if XE991 affects ERG potassium channels.
Main Methods:
- Experiments conducted in Xenopus laevis oocytes expressing ERG1-2 channels.
- Experiments performed in HEK293 cells stably expressing ERG1 channels.
- Characterization of XE991 inhibition using dose-response relationships.
Main Results:
- XE991 inhibits ERG1-2 channels in the micromolar range (EC50 = 107 μM for ERG1).
- KCNQ channel block by XE991 has IC50 values ranging from 1-65 μM.
- XE991 exhibits non-selective inhibition of both KCNQ and ERG channels.
Conclusions:
- XE991 is not a completely selective KCNQ channel blocker.
- Caution is advised when using XE991 concentrations to study native potassium channels.
- Experimental design must account for potential ERG channel inhibition by XE991.
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