Effect of the I(to) activator NS5806 on cloned K(V)4 channels depends on the accessory protein KChIP2.

British Journal of Pharmacology
Alicia LundbyKirstine Calloe

Abstract

The compound NS5806 increases the transient outward current (I(to)) in canine ventricular cardiomyocytes and slows current decay. In human and canine ventricle, I(to) is thought to be mediated by K(V)4.3 and various ancillary proteins, yet, the exact subunit composition of I(to) channels is still debated. Here we characterize the effect of NS5806 on heterologously expressed putative I(to) channel subunits and other potassium channels. Cloned K(V)4 channels were co-expressed with KChIP2, DPP6, DPP10, KCNE2, KCNE3 and K(V)1.4 in Xenopus laevis oocytes or CHO-K1 cells. NS5806 increased K(V)4.3/KChIP2 peak current amplitudes with an EC(50) of 5.3 +/- 1.5microM and significantly slowed current decay. KCNE2, KCNE3, DPP6 and DPP10 modulated K(V)4.3 currents and the response to NS5806, but current decay was slowed only in complexes containing KChIP2. The effect of NS5806 on K(V)4.2 was similar to that on K(V)4.3, and current decay was only slowed in presence of KChIP2. However, for K(V)4.1, the slowing of current decay by NS5806 was independent of KChIP2. K(V)1.4 was strongly inhibited by 10 microM NS5806 and K(V)1.5 was inhibited to a smaller extent. Effects of NS5806 on kinetics of currents generated by K(V)4.3/KChIP2/DPP6 with K(V)1...Continue Reading

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Citations

Feb 13, 2013·Cardiovascular Research·Morten Salling OlesenKirstine Calloe
Nov 2, 2014·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Mary M MaleckarKirstine Calloe
Oct 9, 2013·The Journal of Physiology·Tobias SpeerschneiderMorten B Thomsen
Sep 12, 2012·Neuropharmacology·Katrin WitzelRobert Bähring
Apr 1, 2014·Journal of Cardiovascular Electrophysiology·Søren GrubbKirstine Calloe
Jun 5, 2015·Channels·Martin Nybo AndersenThomas Jespersen
Mar 6, 2015·Scientific Reports·Gustavo Arruda BezerraKarl Gruber
Aug 16, 2013·Journal of Cellular and Molecular Medicine·Jingwei ShengPhilip Wong
Apr 3, 2014·Physiological Reviews·Nicole SchmittSøren-Peter Olesen
Aug 26, 2015·Journal of Biomolecular Screening·Edward S A Humphries, Caroline Dart
Feb 4, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Tatsuya SatoNoritsugu Tohse
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hongxue ZhangYanfang Xu
Feb 13, 2021·International Journal of Molecular Sciences·Pilar CercósMarta Gutiérrez-Rodríguez
Mar 24, 2016·Biochemical Pharmacology·Kirstine CalloeJonathan M Cordeiro

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