on October 3, 2005
Published online before print October 3, 2005, doi: 10.1161/CIRCULATIONAHA.104.527325
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on December 2, 2004
From the Institute for Cardiovascular Research, State University of New York Upstate Medical University, Syracuse. * To whom correspondence should be addressed. E-mail: jalifej{at}upstate.edu.
Background--Intercellular coupling via connexin40 (Cx40) gap junction channels is an important determinant of impulse propagation in the atria. Methods and Results--We studied the role of Cx40 in intra-atrial excitation and propagation in wild-type (Cx40+/+) and knockout (Cx40-/-) mice using high-resolution, dual-wavelength optical mapping. On ECG, the P wave was significantly prolonged in Cx40-/- mice (13.4±0.5 versus 11.4±0.3 ms in Cx40+/+). In Cx40+/+ hearts, spontaneous right atrial (RA) activation showed a focal breakthrough at the junction of the right superior vena cava, sulcus terminalis, and RA free wall, corresponding to the location of the sinoatrial node. In contrast, Cx40-/- hearts displayed ectopic breakthrough sites at the base of the sulcus terminalis, RA free wall, and right superior vena cava. Progressive ablation of such sites in 4 Cx40-/- mice resulted in ectopic focus migration and cycle length prolongation. In all Cx40-/- hearts the focus ultimately shifted to the sinoatrial node at a very prolonged cycle length (initial ectopic cycle length, 182±20 ms; postablation sinus cycle length, 387±44 ms). In a second group of experiments, epicardial pacing at 10 Hz revealed slower conduction in the RA free wall of 5 Cx40-/- hearts than in 5 Cx40+/+ hearts (0.61±0.07 versus 0.94±0.07 m/s; P<0.05). Dominant frequency analysis in Cx40-/- RA demonstrated significant reduction in the area of 1:1 conduction at 16 Hz (40±10% versus 69±5% in Cx40+/+) and 25 Hz (36±11% versus 65±9% in Cx40+/+). Conclusions--This is the first demonstration of intra-atrial block, ectopic rhythms, and altered atrial propagation in the RA of Cx40-/- mice.
Revised on July 11, 2005
Accepted on July 20, 2005
Altered Right Atrial Excitation and Propagation in Connexin40 Knockout Mice
Suveer Bagwe MD, MSc,
Key words: atrium • conduction • connexins • Fourier analysis • sinoatrial node
This article has been cited by other articles:
 |
|
 |
|
  S.-M. Chaldoupi, P. Loh, R. N.W. Hauer, J. M.T. de Bakker, and H. V.M. van Rijen The role of connexin40 in atrial fibrillation Cardiovasc Res, October 1, 2009; 84(1): 15 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J.D. Boukens, V. M. Christoffels, R. Coronel, and A. F.M. Moorman Developmental Basis for Electrophysiological Heterogeneity in the Ventricular and Outflow Tract Myocardium As a Substrate for Life-Threatening Ventricular Arrhythmias Circ. Res., January 2, 2009; 104(1): 19 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. S. Almeida, A. Cordeiro, D. S. Machado, L. L. Souza, T. M. Ortiga-Carvalho, A. C. Campos-de-Carvalho, F. E. Wondisford, and C. C. Pazos-Moura Connexin40 Messenger Ribonucleic Acid Is Positively Regulated by Thyroid Hormone (TH) Acting in Cardiac Atria via the TH Receptor Endocrinology, January 1, 2009; 150(1): 546 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Leaf, J. E. Feig, C. Vasquez, P. L. Riva, C. Yu, J. M. Lader, A. Kontogeorgis, E. L. Baron, N. S. Peters, E. A. Fisher, et al. Connexin40 Imparts Conduction Heterogeneity to Atrial Tissue Circ. Res., October 24, 2008; 103(9): 1001 - 1008. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Lisewski, Y. Shi, U. Wrackmeyer, R. Fischer, C. Chen, A. Schirdewan, R. Juttner, F. Rathjen, W. Poller, M. H. Radke, et al. The tight junction protein CAR regulates cardiac conduction and cell-cell communication J. Exp. Med., September 29, 2008; 205(10): 2369 - 2379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cerrone, S. F. Noujaim, E. G. Tolkacheva, A. Talkachou, R. O'Connell, O. Berenfeld, J. Anumonwo, S. V. Pandit, K. Vikstrom, C. Napolitano, et al. Arrhythmogenic Mechanisms in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia Circ. Res., November 9, 2007; 101(10): 1039 - 1048. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T.M. Mommersteeg, N. A. Brown, O. W.J. Prall, C. de Gier-de Vries, R. P. Harvey, A. F.M. Moorman, and V. M. Christoffels Pitx2c and Nkx2-5 Are Required for the Formation and Identity of the Pulmonary Myocardium Circ. Res., October 26, 2007; 101(9): 902 - 909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. E. Bondarenko and R. L. Rasmusson Simulations of propagated mouse ventricular action potentials: effects of molecular heterogeneity Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1816 - H1832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. M.H. Hoogaars, A. Engel, J. F. Brons, A. O. Verkerk, F. J. de Lange, L.Y. E. Wong, M. L. Bakker, D. E. Clout, V. Wakker, P. Barnett, et al. Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atria Genes & Dev., May 1, 2007; 21(9): 1098 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T.M. Mommersteeg, W. M.H. Hoogaars, O. W.J. Prall, C. de Gier-de Vries, C. Wiese, D. E.W. Clout, V. E. Papaioannou, N. A. Brown, R. P. Harvey, A. F.M. Moorman, et al. Molecular Pathway for the Localized Formation of the Sinoatrial Node Circ. Res., February 16, 2007; 100(3): 354 - 362. [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]
|
|
|
|
|
|
P. Beauchamp, K. A. Yamada, A. J. Baertschi, K. Green, E. M. Kanter, J. E. Saffitz, and A. G. Kleber Relative Contributions of Connexins 40 and 43 to Atrial Impulse Propagation in Synthetic Strands of Neonatal and Fetal Murine Cardiomyocytes Circ. Res., November 24, 2006; 99(11): 1216 - 1224. [Abstract] [Full Text] [PDF]
|
|