This Article Full Text Full Text (PDF) Supplemental File All Versions of this Article: biophysj.105.060459v1 88/6/3806    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pandit, S. V. Articles by Jalife, J. Search for Related Content PubMed PubMed Citation Articles by Pandit, S. V. Articles by Jalife, J.

Ionic Determinants of Functional Reentry in a 2-D Model of Human Atrial Cells During Simulated Chronic Atrial Fibrillation

Sandeep V. Pandit ^*, Omer Berenfeld ^*, Justus M. B. Anumonwo, Roman M. Zaritski , James Kneller , Stanley Nattel  and José Jalife ^*

^* Institute for Cardiovascular Research and Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, New York; Department of Computer Science, Montclair State University, New Jersey; and Montreal Heart Institute, University of Montreal, Montreal, Quebec, Canada H1T 1C8

Correspondence: Address reprint requests to Dr. José Jalife, Institute for Cardiovascular Research and Dept. of Pharmacology, State University of New York Upstate Medical University, Syracuse, NY 13210. Tel.: 315-464-7949; Fax: 315-464-8000; E-mail: jalifej{at}upstate.edu.

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 cm²) of human atrial cells to create a chronic AF substrate, which was able to sustain a stable rotor (dominant frequency 5.7 Hz, rosette-like tip meander 2.6 cm). Doubling the magnitude of the inward rectifier K⁺ current (I_K1) increased rotor frequency (8.4 Hz), and reduced tip meander (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.

This article has been cited by other articles:

				R. Gomez, L. Nunez, M. Vaquero, I. Amoros, A. Barana, T. de Prada, C. Macaya, L. Maroto, E. Rodriguez, R. Caballero, et al. Nitric oxide inhibits Kv4.3 and human cardiac transient outward potassium current (Ito1) Cardiovasc Res, August 24, 2008; (2008) cvn205v2. [Abstract] [Full Text] [PDF]

				U. Ravens and E. Cerbai Role of potassium currents in cardiac arrhythmias Europace, July 24, 2008; (2008) eun193v1. [Abstract] [Full Text] [PDF]

				N. Voigt, A. Maguy, Y.-H. Yeh, X. Qi, U. Ravens, D. Dobrev, and S. Nattel Changes in IK,ACh single-channel activity with atrial tachycardia remodelling in canine atrial cardiomyocytes Cardiovasc Res, January 1, 2008; 77(1): 35 - 43. [Abstract] [Full Text] [PDF]

				S. F. Noujaim, S. V. Pandit, O. Berenfeld, K. Vikstrom, M. Cerrone, S. Mironov, M. Zugermayr, A. N. Lopatin, and J. Jalife Up-regulation of the inward rectifier K+ current (IK1) in the mouse heart accelerates and stabilizes rotors J. Physiol., January 1, 2007; 578(1): 315 - 326. [Abstract] [Full Text] [PDF]

				L. Nunez, M. Vaquero, R. Gomez, R. Caballero, P. Mateos-Caceres, C. Macaya, I. Iriepa, E. Galvez, A. Lopez-Farre, J. Tamargo, et al. Nitric oxide blocks hKv1.5 channels by S-nitrosylation and by a cyclic GMP-dependent mechanism Cardiovasc Res, October 1, 2006; 72(1): 80 - 89. [Abstract] [Full Text] [PDF]

				T.-J. Cha, J. R. Ehrlich, D. Chartier, X.-Y. Qi, L. Xiao, and S. Nattel Kir3-Based Inward Rectifier Potassium Current: Potential Role in Atrial Tachycardia Remodeling Effects on Atrial Repolarization and Arrhythmias Circulation, April 11, 2006; 113(14): 1730 - 1737. [Abstract] [Full Text] [PDF]

				D. Dobrev, A. Friedrich, N. Voigt, N. Jost, E. Wettwer, T. Christ, M. Knaut, and U. Ravens The G Protein-Gated Potassium Current IK,ACh Is Constitutively Active in Patients With Chronic Atrial Fibrillation Circulation, December 13, 2005; 112(24): 3697 - 3706. [Abstract] [Full Text] [PDF]

				R. Zou, J. Kneller, L. J. Leon, and S. Nattel Substrate size as a determinant of fibrillatory activity maintenance in a mathematical model of canine atrium Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1002 - H1012. [Abstract] [Full Text] [PDF]