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
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
-
Online-Ressource
- Sprache
-
Englisch
- Anmerkungen
-
EMBO molecular medicine. - 9, 4 (2017) , 403-414, ISSN: 1757-4676
- Klassifikation
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Medizin, Gesundheit
- Ereignis
-
Veröffentlichung
- (wo)
-
Freiburg
- (wer)
-
Universität
- (wann)
-
2019
- Urheber
-
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
- Beteiligte Personen und Organisationen
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Institut für Experimentelle Kardiovaskuläre Medizin
- DOI
-
10.15252/emmm.201606690
- URN
-
urn:nbn:de:bsz:25-freidok-1365678
- Rechteinformation
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
-
25.03.2025, 13:51 MEZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- 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
- Institut für Experimentelle Kardiovaskuläre Medizin
- Universität
Entstanden
- 2019
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