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Ionic determinants of functional reentry in a 2-D model of human atrial cells during simulated chronic atrial fibrillation.
- Source :
-
Biophysical journal [Biophys J] 2005 Jun; Vol. 88 (6), pp. 3806-21. Date of Electronic Publication: 2005 Mar 25. - Publication Year :
- 2005
-
Abstract
- Recent studies suggest that atrial fibrillation (AF) is maintained by fibrillatory conduction emanating from a small number of high-frequency reentrant sources (rotors). Our goal was to study the ionic correlates of a rotor during simulated chronic AF conditions. We utilized a two-dimensional (2-D), homogeneous, isotropic sheet (5 x 5 cm(2)) of human atrial cells to create a chronic AF substrate, which was able to sustain a stable rotor (dominant frequency approximately 5.7 Hz, rosette-like tip meander approximately 2.6 cm). Doubling the magnitude of the inward rectifier K(+) current (I(K1)) increased rotor frequency ( approximately 8.4 Hz), and reduced tip meander (approximately 1.7 cm). This rotor stabilization was due to a shortening of the action potential duration and an enhanced cardiac excitability. The latter was caused by a hyperpolarization of the diastolic membrane potential, which increased the availability of the Na(+) current (I(Na)). The rotor was terminated by reducing the maximum conductance (by 90%) of the atrial-specific ultrarapid delayed rectifier K(+) current (I(Kur)), or the transient outward K(+) current (I(to)), but not the fast or slow delayed rectifier K(+) currents (I(Kr)/I(Ks)). Importantly, blockade of I(Kur)/I(to) prolonged the atrial action potential at the plateau, but not at the terminal phase of repolarization, which led to random tip meander and wavebreak, resulting in rotor termination. Altering the rectification profile of I(K1) also slowed down or abolished reentrant activity. In combination, these simulation results provide novel insights into the ionic bases of a sustained rotor in a 2-D chronic AF substrate.
- Subjects :
- Action Potentials
Anti-Arrhythmia Agents pharmacology
Atrial Fibrillation drug therapy
Biophysical Phenomena
Biophysics
Calcium Channels, L-Type physiology
Chronic Disease
Humans
In Vitro Techniques
Potassium Channel Blockers pharmacology
Potassium Channels physiology
Sodium Channels physiology
Atrial Fibrillation physiopathology
Ion Channels physiology
Models, Cardiovascular
Myocytes, Cardiac physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3495
- Volume :
- 88
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Biophysical journal
- Publication Type :
- Academic Journal
- Accession number :
- 15792974
- Full Text :
- https://doi.org/10.1529/biophysj.105.060459