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Cardiovascular Research 1999 44(1):121-131; doi:10.1016/S0008-6363(99)00178-9
© 1999 by European Society of Cardiology
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Copyright © 1999, European Society of Cardiology

Ionic mechanisms of electrical remodeling in human atrial fibrillation

Ralph F. Bosch*, Xiaorong Zeng, Joachim B. Grammer, Katarina Popovic, Christian Mewis and Volker Kühlkamp

Department of Cardiology, University of Tübingen, Tübingen, Germany

* Corresponding author. Tel.: +49-7071-298-3196; fax: +49-7071-295-285 ralph.bosch{at}uni-tuebingen.de

Objectives: Atrial fibrillation (AF) is associated with a decrease in atrial ERP and ERP adaptation to rate as well as changes in atrial conduction velocity. The cellular changes in repolarization and the underlying ionic mechanisms in human AF are only poorly understood. Methods: Action potentials (AP) and ionic currents were studied with the patch clamp technique in single atrial myocytes from patients in chronic AF and compared to those from patients in stable sinus rhythm (SR). Results: The presence of AF was associated with a marked shortening of the AP duration and a decreased rate response of atrial repolarization. L-type calcium current (ICa,L) and the transient outward current (Ito) were both reduced about 70% in AF, whereas an increased steady-state outward current was detectable at test potentials between –30 and 0 mV. The inward rectifier potassium current (IK1) and the acetylcholine-activated potassium current (IKACh) were increased in AF at hyperpolarizing potentials. Voltage-dependent inactivation of the fast sodium current (INa) was shifted to more positive voltages in AF. Conclusions: AF in humans leads to important changes in atrial potassium and calcium currents that likely contribute to the decrease in APD and APD rate adaptation. These changes contribute to electrical remodeling in AF and are therefore important factors for the perpetuation of the arrhythmia.

KEYWORDS Experimental; Heart; Cellular; Electrophysiology; Arrhythmia (mechanisms); Ca-channel; K-channel; Na-channel; Ion channels


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B. J. J. M. Brundel, I. C. Van Gelder, R. H. Henning, R. G. Tieleman, A. E. Tuinenburg, M. Wietses, J. G. Grandjean, W. H. Van Gilst, and H. J. G. M. Crijns
Ion Channel Remodeling Is Related to Intraoperative Atrial Effective Refractory Periods in Patients With Paroxysmal and Persistent Atrial Fibrillation
Circulation, February 6, 2001; 103(5): 684 - 690.
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CirculationHome page
U. Schotten, J. Ausma, C. Stellbrink, I. Sabatschus, M. Vogel, D. Frechen, F. Schoendube, P. Hanrath, and M. A. Allessie
Cellular Mechanisms of Depressed Atrial Contractility in Patients With Chronic Atrial Fibrillation
Circulation, February 6, 2001; 103(5): 691 - 698.
[Abstract] [Full Text] [PDF]


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CirculationHome page
M. A. Allessie, P. A. Boyden, A. J. Camm, A. G. Kleber, M. J. Lab, M. J. Legato, M. R. Rosen, P. J. Schwartz, P. M. Spooner, D. R. Van Wagoner, et al.
Pathophysiology and Prevention of Atrial Fibrillation
Circulation, February 6, 2001; 103(5): 769 - 777.
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Circ. Res.Home page
S. Nattel and D. Li
Ionic Remodeling in the Heart : Pathophysiological Significance and New Therapeutic Opportunities for Atrial Fibrillation
Circ. Res., September 15, 2000; 87(6): 440 - 447.
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CirculationHome page
D. Dobrev, E. Wettwer, H. M. Himmel, A. Kortner, E. Kuhlisch, S. Schuler, W. Siffert, and U. Ravens
G-Protein {beta}3-Subunit 825T Allele Is Associated With Enhanced Human Atrial Inward Rectifier Potassium Currents
Circulation, August 8, 2000; 102(6): 692 - 697.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
M. A Allessie
Atrial fibrillation-induced electrical remodeling in humans: What is the next step?
Cardiovasc Res, October 1, 1999; 44(1): 10 - 12.
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