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Transcriptional regulation of the TASK-1 potassium channel by ETV1: Implications for atrial excitability

Background - Atrial fibrillation (AF), the most common sustained arrhythmia, is driven by electrical and structural remodelling, including altered ion channel expression. The atrial-specific potassium channel TASK-1 regulates action potential duration (APD) and is differentially expressed in AF and...

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Autores principales: Beck, Moritz (Autor) , Wiedmann, Felix Tobias (Autor) , Kraft, Manuel (Autor) , Laurette, Patrick (Autor) , Paasche, Amelie (Autor) , Lanzer, Jan David (Autor) , Jamros, Max (Autor) , Malchin, Ciara (Autor) , Ziehmer, Paul Henri (Autor) , Goetz, Christian (Autor) , Zaradzki, Marcin (Autor) , Arif, Rawa (Autor) , Karck, Matthias (Autor) , Frey, Norbert (Autor) , Gilsbach, Ralf (Autor) , Schmidt, Constanze (Autor)
Formato: Article (Journal)
Lenguaje:inglés
Publicado: September 2026
In: Journal of molecular and cellular cardiology
Year: 2026, Volumen: 218, Pages: 111-120
ISSN:1095-8584
DOI:10.1016/j.yjmcc.2026.07.009
Acceso en línea:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.yjmcc.2026.07.009
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0022282826001057
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Notas de Autor:Moritz Beck, Felix Wiedmann, Manuel Kraft, Patrick Laurette, Amelie Paasche, Jan Lanzer, Max Jamros, Ciara Malchin, Paul Henri Ziehmer, Christian Goetz, Marcin Zaradzki, Arif Rawa, Matthias Karck, Norbert Frey, Ralf Gilsbach, Constanze Schmidt
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Sumario:Background - Atrial fibrillation (AF), the most common sustained arrhythmia, is driven by electrical and structural remodelling, including altered ion channel expression. The atrial-specific potassium channel TASK-1 regulates action potential duration (APD) and is differentially expressed in AF and left ventricular dysfunction, but the mechanisms controlling its expression are not well understood. - Objective - This study examines whether the transcription factor ETV1 regulates TASK-1 and contributes to atrial electrical remodelling. - Methods - Atrial tissue from patients with and without AF was analysed to assess the relationship between ETV1 and TASK-1 (KCNK3) expression. In HL-1 cardiomyocyte-like cells and native fibroblasts, ETV1 activity was reduced using pharmacological inhibition or siRNA-mediated knockdown. TASK-1 expression, TASK-1 current, and APD at 90% repolarization were measured. Pacing experiments tested activity-dependent TASK-1 regulation. Direct transcriptional regulation was evaluated using ChIP-qPCR and ChIP-seq to detect ETV1 binding at the KCNK3 promoter. - Results - ETV1 and TASK-1 levels were positively correlated in human atrial tissue. In HL-1 cells and fibroblasts, ETV1 inhibition or knockdown decreased TASK-1 expression and current and selectively prolonged APD90. Pacing-induced upregulation of TASK-1 was prevented by ETV1 inhibition, indicating a protective effect against pro-arrhythmic remodelling. ChIP-qPCR and ChIP-seq confirmed direct ETV1 binding to the KCNK3 promoter. - Conclusion - ETV1 directly regulates TASK-1 expression and contributes to atrial electrical remodelling, identifying ETV1 as a potential upstream therapeutic target in AF.
Notas:Onlineveröffentlicht: 30. Juli 2026, Artikelversion: 13. August 2026
Gesehen am 07.09.2026
Descripción Física:Online Resource
ISSN:1095-8584
DOI:10.1016/j.yjmcc.2026.07.009

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