Sodium permeable and “hypersensitive” TREK‐1 channels cause ventricular tachycardia
نویسندگان
چکیده
In a patient with right ventricular outflow tract (RVOT) tachycardia, we identified a heterozygous point mutation in the selectivity filter of the stretch-activated K2P potassium channel TREK-1 (KCNK2 or K2P2.1). 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 K2P channel stretch-activation and the role of TREK-1 in mechano-electrical feedback in the heart.
منابع مشابه
Sodium leak through K2P potassium channels and cardiac arrhythmia, an emerging theme
In this issue of EMBO Molecular Medicine, Decher et al (2017) identify a point mutation in the K2P2 (TREK-1) potassium (K) channel that changes function in just those ways expected to predispose to right ventricular outflow tract (RVOT) ventricular tachycardia (VT) in the patient they study. Whereas wild-type channels are selective for K and inhibited by b-adrenergic stimulation, mutant I267T c...
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عنوان ژورنال:
دوره 9 شماره
صفحات -
تاریخ انتشار 2017