@misc{10481/76989,
year = {2022},
month = {8},
url = {https://hdl.handle.net/10481/76989},
abstract = {The transient outward potassium current (Itof) is generated by the activation of KV4 channels
assembled with KChIP2 and other accessory subunits (DPP6 and KCNE2). To test the hypothesis
that these subunits modify the channel pharmacology, we analyzed the electrophysiological effects
of (3-(2-(3-phenoxyphenyl)acetamido)-2-naphthoic acid) (IQM-266), a new KChIP2 ligand, on the
currents generated by KV4.3/KChIP2, KV4.3/KChIP2/DPP6 and KV4.3/KChIP2/KCNE2 channels.
CHO cells were transiently transfected with cDNAs codifying for different proteins (KV4.3/KChIP2,
KV4.3/KChIP2/DPP6 or KV4.3/KChIP2/KCNE2), and the potassium currents were recorded using
the whole-cell patch-clamp technique. IQM-266 decreased the maximum peak of KV4.3/KChIP2,
KV4.3/KChIP2/DPP6 and KV4.3/KChIP2/KCNE2 currents, slowing their time course of inactivation
in a concentration-, voltage-, time- and use-dependent manner. IQM-266 produced an increase in
the charge in KV4.3/KChIP2 channels that was intensified when DPP6 was present and abolished
in the presence of KCNE2. IQM-266 induced an activation unblocking effect during the application
of trains of pulses to cells expressing KV4.3/KChIP2 and KV4.3/KChIP2/KCNE2, but not in
KV4.3/KChIP2/DPP6 channels. Overall, all these results are consistent with a preferential IQM-266
binding to an active closed state of Kv4.3/KChIP2 and Kv4.3/KChIP2/KCNE2 channels, whereas in
the presence of DPP6, IQM-266 binds preferentially to an inactivated state. In conclusion, DPP6 and
KCNE2 modify the pharmacological response of KV4.3/KChIP2 channels to IQM-266.},
organization = {MCIN/AEI	SAF2016-75021-R	
RTI2018-097189-B-C22	
BIO2017-89523-R	
PID2019-104366RB-C21	
PID2019-104366RB-C22	
PID2020-114256RB-I00	
PID2020-119805RB-I00	
BES-2017-080184	
BES-2010-036573	
PRE2018-083280	
RYC2018-023837-I},
organization = {ERDF A way of making Europe	SAF2016-75021-R	
RTI2018-097189-B-C22	
BIO2017-89523-R},
organization = {FEDER/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento	A-FQM-386-UGR20},
organization = {Instituto de Salud Carlos III CIBERCV	CB/11/00222},
organization = {Consejo Superior de Investigaciones Cientificas	PIE202180E073	
PIE201820E104	
2019AEP148},
organization = {ESF Investing in your future	BES-2017-080184	
BES-2010-036573	
PRE2018-083280	
RYC2018-023837-I},
organization = {Instituto de Salud Carlos III},
organization = {Spanish Government},
organization = {European Commission	FPU17/02731},
publisher = {MDPI},
keywords = {KV4 channels},
keywords = {KChIP2},
keywords = {DPP6},
keywords = {KCNE},
keywords = {KChIP2 ligand},
title = {Modulation of KV4.3-KChIP2 Channels by IQM-266: Role of DPP6 and KCNE2},
doi = {10.3390/ijms23169170},
author = {De Benito Bueno, Ángela and Marín Olivero, Irene and Pérez Lara, Francisco Ángel and González Vera, Juan Antonio and Orte Gutiérrez, Ángel},
}