Modulation of ERG channels by XE991.
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.
Elmedyb
Pernille
P
Department of Medical Physiology, The Panum Institute, The University of Copenhagen, Denmark.
Calloe
Kirstine
K
Schmitt
Nicole
N
Hansen
Rie Schultz
RS
Grunnet
Morten
M
Olesen
Søren-Peter
SP
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D002219:Carbamates / Q000494:pharmacology; D002460:Cell Line; D002839:Chromans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000072237:ERG1 Potassium Channel; D004594:Electrophysiology; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D007211:Indoles / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010655:Phenylenediamines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D014982:Xenopus laevis
C112297:10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone; D000873:Anthracenes; D002219:Carbamates; D002839:Chromans; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D007211:Indoles; C109500:Kcnh6 protein, rat; D010655:Phenylenediamines; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D011725:Pyridines; C101866:ezogabine; C029141:2,2,5,7,8-pentamethyl-1-hydroxychroman; C061017:linopirdine; D000109:Acetylcholine