Open AccessSodium permeable and “hypersensitive” TREK ‐1 channels cause ventricular tachycardia
Author(s) -
Decher Niels,
OrtizBonnin Beatriz,
Friedrich Corinna,
Schewe Marcus,
Kiper Aytug K,
Rinné Susanne,
Seemann Gunnar,
Peyronnet Rémi,
Zumhagen Sven,
Bustos Daniel,
Kockskämper Jens,
Kohl Peter,
Just Steffen,
González Wendy,
Baukrowitz Thomas,
Stallmeyer Birgit,
SchulzeBahr Eric
Publication year - 2017
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201606690
Subject(s) - sodium channel , chemistry , potassium channel , sodium , tetrodotoxin , sodium channel blocker , biophysics , medicine , cardiology , biology , organic chemistry
In a patient with right ventricular outflow tract ( RVOT ) tachycardia, we identified a heterozygous point mutation in the selectivity filter of the stretch‐activated K 2P potassium channel TREK ‐1 ( KCNK 2 or K 2P 2.1). This mutation introduces abnormal sodium permeability to TREK ‐1. In addition, mutant channels exhibit a hypersensitivity to stretch‐activation, suggesting that the selectivity filter is directly involved in stretch‐induced activation and desensitization. Increased sodium permeability and stretch‐sensitivity of mutant TREK ‐1 channels may trigger arrhythmias in areas of the heart with high physical strain such as the RVOT . We present a pharmacological strategy to rescue the selectivity defect of the TREK ‐1 pore. Our findings provide important insights for future studies of K 2P channel stretch‐activation and the role of TREK ‐1 in mechano‐electrical feedback in the heart.