Send to

Choose Destination
Eur Heart J. 2017 Jun 7;38(22):1764-1774. doi: 10.1093/eurheartj/ehw559.

Inverse remodelling of K2P3.1 K+ channel expression and action potential duration in left ventricular dysfunction and atrial fibrillation: implications for patient-specific antiarrhythmic drug therapy.

Author information

Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
DZHK (German Center for Cardiovascular Research), partner site Heidelberg/Mannheim, University of Heidelberg, Heidelberg, Germany.
First Department of Medicine, University Medical Center Mannheim, Mannheim, Germany.
Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Essen, Germany.
Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Georg-August University Göttingen, Göttingen, Germany.
DZHK (German Center for Cardiovascular Research), Göttingen, Germany, partner site.
Department for Bioinformatics and Functional Genomics, Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Institute for Pharmacy and Molecular Biotechnology (IPMB) and BioQuant, Heidelberg University, Heidelberg, Germany.
Department of Cardiac Surgery, University Hospital Heidelberg, Heidelberg, Germany.
INCCI Haerzzenter, Institut National de Chirurgie Cardiaque et de Cardiologie Interventionnelle, Luxembourg, Luxembourg.
Department of Cardiology, Internal Medicine III, Goethe University, Frankfurt, Germany.
Department of Cardiology, St. Josefs-Hospital, Wiesbaden, Germany.
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Institute of Physiology, Medical Faculty, TU Dresden, Dresden, Germany.



Atrial fibrillation (AF) prevalence increases with advanced stages of left ventricular (LV) dysfunction. Remote proarrhythmic effects of ventricular dysfunction on atrial electrophysiology remain incompletely understood. We hypothesized that repolarizing K2P3.1 K+ channels, previously implicated in AF pathophysiology, may contribute to shaping the atrial action potential (AP), forming a specific electrical substrate with LV dysfunction that might represent a target for personalized antiarrhythmic therapy.

Methods and results:

A total of 175 patients exhibiting different stages of LV dysfunction were included. Ion channel expression was quantified by real-time polymerase chain reaction and Western blot. Membrane currents and APs were recorded from atrial cardiomyocytes using the patch-clamp technique. Severely reduced LV function was associated with decreased atrial K2P3.1 expression in sinus rhythm patients. In contrast, chronic (c)AF resulted in increased K2P3.1 levels, but paroxysmal (p)AF was not linked to significant K2P3.1 remodelling. LV dysfunction-related suppression of K2P3.1 currents prolonged atrial AP duration (APD) compared with patients with preserved LV function. In individuals with concomitant LV dysfunction and cAF, APD was determined by LV dysfunction-associated prolongation and by cAF-dependent shortening, respectively, consistent with changes in K2P3.1 abundance. K2P3.1 inhibition attenuated APD shortening in cAF patients irrespective of LV function, whereas in pAF subjects with severely reduced LV function, K2P3.1 blockade resulted in disproportionately high APD prolongation.


LV dysfunction is associated with reduction of atrial K2P3.1 channel expression, while cAF leads to increased K2P3.1 abundance. Differential remodelling of K2P3.1 and APD provides a basis for patient-tailored antiarrhythmic strategies.


Arrhythmia ; Atrial fibrillation ; Electrical remodelling ; Electrophysiology ; Heart failure ; K2P3.1 channel

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center