Sodium permeable and “hypersensitive” TREK‐1 channels cause ventricular tachycardia

Abstract: 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

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: EMBO molecular medicine. - 9, 4 (2017) , 403-414, ISSN: 1757-4676

Classification and Topics

• Classification: Medizin, Gesundheit

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2019
• Creator: Decher, Niels ; Ortiz Bonnin, Beatriz ; Friedrich, Corinna ; Schewe, Marcus ; Kiper, Aytuğ ; Rinné, Susanne ; Seemann, Gunnar ; Peyronnet, Remi ; Zumhagen, Sven ; Bustos, Daniel ; Kockskämper, Jens ; Kohl, Peter ; Just, Steffen ; Gonzalez, Wendy ; Baukrowitz, Thomas ; Stallmeyer, Birgit ; Schulze-Bahr, Eric
• Contributor: Institut für Experimentelle Kardiovaskuläre Medizin

Further information

• DOI: 10.15252/emmm.201606690
• URN: urn:nbn:de:bsz:25-freidok-1365678
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:51 PM CET