Schmidt, C. and Wiedmann, F. and Zhou, X. B. and Heijman, J. and Voigt, N. and Szabó, Gábor Balázs and Baczkó, István (2017) 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. EUROPEAN HEART JOURNAL, 38 (2). pp. 1764-1774. ISSN 0195-668X
|
Text
Schmidt_Baczko_EurHJ2017.pdf Download (1MB) | Preview |
Official URL: http://doi.org/10.1093/eurheartj/ehw559
Abstract
AIMS: 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. CONCLUSION: 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.
| Item Type: | Article |
|---|---|
| Additional 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, Netherlands Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Georg-August University Göttingen, Göttingen, Germany DZHK (German Center for Cardiovascular Research), Göttingen, Germany 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 Institute of Experimental Cardiovascular Medicine, University Heart Center Freiburg, Bad Krozingen, Freiburg, Germany Cited By :28 Export Date: 10 December 2019 CODEN: EHJOD Correspondence Address: Thomas, D.; Department of Cardiology, University of HeidelbergGermany; email: dierk.thomas@med.uni-heidelberg.de Chemicals/CAS: Anti-Arrhythmia Agents; Nerve Tissue Proteins; potassium channel subfamily K member 3; Potassium Channels, Tandem Pore Domain 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, Netherlands Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Georg-August University Göttingen, Göttingen, Germany DZHK (German Center for Cardiovascular Research), Göttingen, Germany 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 Institute of Experimental Cardiovascular Medicine, University Heart Center Freiburg, Bad Krozingen, Freiburg, Germany Cited By :29 Export Date: 23 January 2020 CODEN: EHJOD Correspondence Address: Thomas, D.; Department of Cardiology, University of HeidelbergGermany; email: dierk.thomas@med.uni-heidelberg.de Chemicals/CAS: Anti-Arrhythmia Agents; Nerve Tissue Proteins; potassium channel subfamily K member 3; Potassium Channels, Tandem Pore Domain 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, Netherlands Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Georg-August University Göttingen, Göttingen, Germany DZHK (German Center for Cardiovascular Research), Göttingen, Germany 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 Institute of Experimental Cardiovascular Medicine, University Heart Center Freiburg, Bad Krozingen, Freiburg, Germany Cited By :29 Export Date: 19 February 2020 CODEN: EHJOD Correspondence Address: Thomas, D.; Department of Cardiology, University of HeidelbergGermany; email: dierk.thomas@med.uni-heidelberg.de Chemicals/CAS: Anti-Arrhythmia Agents; Nerve Tissue Proteins; potassium channel subfamily K member 3; Potassium Channels, Tandem Pore Domain 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, Netherlands Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Georg-August University Göttingen, Göttingen, Germany DZHK (German Center for Cardiovascular Research), Göttingen, Germany 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 Institute of Experimental Cardiovascular Medicine, University Heart Center Freiburg, Bad Krozingen, Freiburg, Germany Cited By :36 Export Date: 9 July 2020 CODEN: EHJOD Correspondence Address: Thomas, D.; Department of Cardiology, University of HeidelbergGermany; email: dierk.thomas@med.uni-heidelberg.de Chemicals/CAS: Anti-Arrhythmia Agents; Nerve Tissue Proteins; potassium channel subfamily K member 3; Potassium Channels, Tandem Pore Domain 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, Netherlands Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Georg-August University Göttingen, Göttingen, Germany DZHK (German Center for Cardiovascular Research), Göttingen, Germany 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 Institute of Experimental Cardiovascular Medicine, University Heart Center Freiburg, Bad Krozingen, Freiburg, Germany Cited By :40 Export Date: 14 October 2020 CODEN: EHJOD Correspondence Address: Thomas, D.; Department of Cardiology, University of HeidelbergGermany; email: dierk.thomas@med.uni-heidelberg.de Chemicals/CAS: Anti-Arrhythmia Agents; Nerve Tissue Proteins; potassium channel subfamily K member 3; Potassium Channels, Tandem Pore Domain |
| Subjects: | R Medicine / orvostudomány > RC Internal medicine / belgyógyászat |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 07 Jan 2021 15:02 |
| Last Modified: | 07 Jan 2021 15:02 |
| URI: | http://real.mtak.hu/id/eprint/119299 |
Actions (login required)
 |
Edit Item |
