| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 The Department of Biomedical Engineering, MetroHealth Campus, Case Western Reserve University, Cleveland, OH, USA
* To whom correspondence should be addressed. E-mail: drosenbaum{at}metrohealht.org.
Recently, we found that electrophysiologic heterogeneities between subepicardial and midmyocardial cells can form a substrate for reentrant ventricular arrhythmias. However, cell-tocell coupling through gap junctions is expected to attenuate transmural heterogeneities between cell types spanning the ventricular wall. Since connexin43 (Cx43) is the principal ventricular gap junction protein, we hypothesized that transmural electrophysiologic heterogeneities are, in part, produced by heterogeneous Cx43 expression across the ventricular wall. Left ventricles of 8 dogs were sectioned in order to expose the transmural surface. To determine if heterogeneous
Cx43 expression influenced electrophysiologic function, high-resolution transmural opticalmapping of the arterially perfused canine wedge preparation was used to measure transmural conduction velocity (
TM), dV/dtmax, transmural space constant (
TM), and transmural gradients of action potential duration (APD). Relative Cx43 expression, quantified by confocal
immunofluorescence, was significantly lower (by 24±17%, p<0.05) in subepicardial compared to deeper layers. Importantly, reduced subepicardial Cx43 was associated with transmural heterogeneities of electrophysiological function evidenced by selectively reduced subepicardial
TM (by 18±9%, p<0.05) compared to deeper layers. dV/dtmax was fastest (by 19±15%) and TM was smallest (by 18.1±2%) in subepicardial regions, suggesting that conduction slowing was attributable to localized uncoupling rather than reduced excitability. The maximum transmural
APD gradients occurred in the same regions where Cx43 expression was lowest, suggesting that Cx43 expression patterns served to maintain APD gradients across the transmural wall. These data demonstrate that heterogeneous Cx43 expression is closely associated with functionally significant electrophysiologic heterogeneities across the transmural wall. Therefore, Cx43 expression patterns can potentially contribute to arrhythmic substrates dependent on
transmural electrophysiologic heterogeneities.
This article has been cited by other articles:
|
|
 |
|
  S. M. Narayan, J. D. Bayer, G. Lalani, and N. A. Trayanova Action Potential Dynamics Explain Arrhythmic Vulnerability in Human Heart Failure: A Clinical and Modeling Study Implicating Abnormal Calcium Handling J. Am. Coll. Cardiol., November 25, 2008; 52(22): 1782 - 1792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Lin, C. Zemlin, J. K. Hennan, J. S. Petersen, and R. D. Veenstra Enhancement of ventricular gap-junction coupling by rotigaptide Cardiovasc Res, August 1, 2008; 79(3): 416 - 426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Cordeiro, M. Mazza, R. Goodrow, N. Ulahannan, C. Antzelevitch, and J. M. Di Diego Functionally distinct sodium channels in ventricular epicardial and endocardial cells contribute to a greater sensitivity of the epicardium to electrical depression Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H154 - H162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Veeraraghavan and S. Poelzing Mechanisms underlying increased right ventricular conduction sensitivity to flecainide challenge Cardiovasc Res, March 1, 2008; 77(4): 749 - 756. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mertens, O. Stiedl, S. Steinlechner, and M. Meyer Cardiac dynamics during daily torpor in the Djungarian hamster (Phodopus sungorus) Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R639 - R650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Kjolbye, M. Dikshteyn, B. C. Eloff, I. Deschenes, and D. S. Rosenbaum Maintenance of intercellular coupling by the antiarrhythmic peptide rotigaptide suppresses arrhythmogenic discordant alternans Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H41 - H49. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. D. Wilson and D. S. Rosenbaum Mechanisms of arrythmogenic cardiac alternans Europace, November 1, 2007; 9(suppl_6): vi77 - vi82. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Colli Franzone, L. F. Pavarino, S. Scacchi, and B. Taccardi Monophasic action potentials generated by bidomain modeling as a tool for detecting cardiac repolarization times Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2771 - H2785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Antzelevitch Role of spatial dispersion of repolarization in inherited and acquired sudden cardiac death syndromes Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2024 - H2038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Jiang, J. M. Guccione, M. B. Ratcliffe, and E. W. Hsu Transmural heterogeneity of diffusion anisotropy in the sheep myocardium characterized by MR diffusion tensor imaging Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2377 - H2384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. E. Tansey, K. F. Kwaku, P. E. Hammer, D. B. Cowan, M. Federman, S. Levitsky, and J. D. McCully Reduction and redistribution of gap and adherens junction proteins after ischemia and reperfusion. Ann. Thorac. Surg., October 1, 2006; 82(4): 1472 - 1479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Fish, J. Brugada, and C. Antzelevitch Potential Proarrhythmic Effects of Biventricular Pacing J. Am. Coll. Cardiol., December 20, 2005; 46(12): 2340 - 2347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Poelzing, B. J. Roth, and D. S. Rosenbaum Optical measurements reveal nature of intercellular coupling across ventricular wall Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1428 - H1435. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cheng, F. Langer, F. Rodriguez, J. C. Criscione, G. T. Daughters, D. C. Miller, and N. B. Ingels Jr. Transmural sheet strains in the lateral wall of the ovine left ventricle Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1234 - H1241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Lin, J. Gemel, E. C. Beyer, and R. D. Veenstra Dynamic model for ventricular junctional conductance during the cardiac action potential Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1113 - H1123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Xue, H. C. Cho, F. G. Akar, S.-Y. Tsang, S. P. Jones, E. Marban, G. F. Tomaselli, and R. A. Li Functional Integration of Electrically Active Cardiac Derivatives From Genetically Engineered Human Embryonic Stem Cells With Quiescent Recipient Ventricular Cardiomyocytes: Insights Into the Development of Cell-Based Pacemakers Circulation, January 4, 2005; 111(1): 11 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Antzelevitch Cardiac repolarization. The long and short of it Europace, January 1, 2005; 7(s2): S3 - S9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Qu Dynamical effects of diffusive cell coupling on cardiac excitation and propagation: a simulation study Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2803 - H2812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. G. Akar, D. D. Spragg, R. S. Tunin, D. A. Kass, and G. F. Tomaselli Mechanisms Underlying Conduction Slowing and Arrhythmogenesis in Nonischemic Dilated Cardiomyopathy Circ. Res., October 1, 2004; 95(7): 717 - 725. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Poelzing and D. S. Rosenbaum Altered connexin43 expression produces arrhythmia substrate in heart failure Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1762 - H1770. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
