© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
Role of gap junctions in the propagation of the cardiac action potential
Department of Physiology, University of Bern, Bühlplatz 5, CH-3012 Bern, Switzerland
* Tel.: +41-31-631-87-46; fax: +41-31-631-46-11. Email address: rohr{at}pyl.unibe.ch
Gap junctions play a pivotal role for the velocity and the safety of impulse propagation in cardiac tissue. Under physiologic conditions, the specific subcellular distribution of gap junctions together with the tight packaging of the rod-shaped cardiomyocytes underlies anisotropic conduction, which is continuous at the macroscopic scale. However, when breaking down the three-dimensional network of cells into linear single cell chains, gap junctions can be shown to limit axial current flow and to induce ‘saltatory’ conduction at unchanged overall conduction velocities. In two- and three-dimensional tissue, these discontinuities disappear due to lateral averaging of depolarizing current flow at the activation wavefront. During gap junctional uncoupling, discontinuities reappear and are accompanied by slowed and meandering conduction. Critical gap junctional uncoupling reduces conduction velocities to a much larger extent than does a reduction of excitability, which suggests that the safety for conduction is higher at any given conduction velocity for gap junctional uncoupling. In uniformly structured tissue, gap junctional uncoupling is accompanied by a parallel decrease in conduction velocity. However, this is not necessarily the case for non-uniform structures like tissue expansion where partial uncoupling paradoxically increases conduction velocity and has the capacity to remove unidirectional conduction blocks. Whereas the impact of gap junctions on impulse conduction is generally assessed from the point of view of cell coupling among cardiomyocytes, it is possible that other cell types within the myocardium might be coupled to cardiomyocytes as well. In this context, it has been shown that fibroblasts establish successful conduction between sheets of cardiomyocytes over distances as long as 300 µm. This might not only explain electrical synchronization of heart transplants but might be of importance for cardiac diseases involving fibrosis. Finally, the intriguing fact that sodium channels are clustered at the intercalated disc recently rekindled the provocative question of whether gap junctions alone are responsible for impulse propagation or whether electric field mechanisms might account for conduction as well. Whereas computer simulations show the feasibility of conduction in the absence of gap junctional coupling, a definite answer to this question must await further investigations into the biophysical properties of the intercalated disc.
KEYWORDS Heart; Impulse propagation; Gap junction; Tissue structure; Sodium channels
Time for primary review 26 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Maass, S. E. Chase, X. Lin, and M. Delmar Cx43 CT domain influences infarct size and susceptibility to ventricular tachyarrhythmias in acute myocardial infarction Cardiovasc Res, December 1, 2009; 84(3): 361 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. O. Grant Cardiac Ion Channels Circ Arrhythm Electrophysiol, April 1, 2009; 2(2): 185 - 194. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Mori, G. I. Fishman, and C. S. Peskin Ephaptic conduction in a cardiac strand model with 3D electrodiffusion PNAS, April 29, 2008; 105(17): 6463 - 6468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. A. M. Kusters, W. P. M. van Meerwijk, D. L. Ypey, A. P. R. Theuvenet, and C. C. A. M. Gielen Fast calcium wave propagation mediated by electrically conducted excitation and boosted by CICR Am J Physiol Cell Physiol, April 1, 2008; 294(4): C917 - C930. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ryu, L. Li, C. M. Khrestian, N. Matsumoto, J. Sahadevan, M. L. Ruehr, D. R. Van Wagoner, I. R. Efimov, and A. L. Waldo Effects of sterile pericarditis on connexins 40 and 43 in the atria: correlation with abnormal conduction and atrial arrhythmias Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H1231 - H1241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Liu, H. Dobrzynski, J. Yanni, M. R. Boyett, and M. Lei Organisation of the mouse sinoatrial node: structure and expression of HCN channels Cardiovasc Res, March 1, 2007; 73(4): 729 - 738. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Pijnappels, M. J. Schalij, J. van Tuyn, D. L. Ypey, A. A.F. de Vries, E. E. van der Wall, A. van der Laarse, and D. E. Atsma Progressive increase in conduction velocity across human mesenchymal stem cells is mediated by enhanced electrical coupling Cardiovasc Res, November 1, 2006; 72(2): 282 - 291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Rucker-Martin, P. Milliez, S. Tan, X. Decrouy, M. Recouvreur, R. Vranckx, C. Delcayre, J.-F. Renaud, I. Dunia, D. Segretain, et al. Chronic hemodynamic overload of the atria is an important factor for gap junction remodeling in human and rat hearts Cardiovasc Res, October 1, 2006; 72(1): 69 - 79. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Baudino, W. Carver, W. Giles, and T. K. Borg Cardiac fibroblasts: friend or foe? Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1015 - H1026. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Hennan, R. E. Swillo, G. A. Morgan, J. C. Keith Jr., R. G. Schaub, R. P. Smith, H. S. Feldman, K. Haugan, J. Kantrowitz, P. J. Wang, et al. Rotigaptide (ZP123) Prevents Spontaneous Ventricular Arrhythmias and Reduces Infarct Size During Myocardial Ischemia/Reperfusion Injury in Open-Chest Dogs J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 236 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Sweitzer, S. A. Fann, T. K. Borg, J. W. Baynes, and M. J. Yost What is the future of diabetic wound care? The Diabetes Educator, March 1, 2006; 32(2): 197 - 210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bagwe, O. Berenfeld, D. Vaidya, G. E. Morley, and J. Jalife Altered Right Atrial Excitation and Propagation in Connexin40 Knockout Mice Circulation, October 11, 2005; 112(15): 2245 - 2253. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. L. Moss, A. D. Fuller, C. L. Sahley, and B. D. Burrell Serotonin Modulates Axo-Axonal Coupling Between Neurons Critical for Learning in the Leech J Neurophysiol, October 1, 2005; 94(4): 2575 - 2589. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Shibayama, W. Paznekas, A. Seki, S. Taffet, E. W. Jabs, M. Delmar, and H. Musa Functional Characterization of Connexin43 Mutations Found in Patients With Oculodentodigital Dysplasia Circ. Res., May 27, 2005; 96(10): e83 - e91. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Rothenberg, V. P. Nikolski, M. Watanabe, and I. R. Efimov Electrophysiology and anatomy of embryonic rabbit hearts before and after septation Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H344 - H351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dhein and H. J Jongsma Forming the network--gap junctions in the cardiovascular system Cardiovasc Res, May 1, 2004; 62(2): 225 - 227. [Full Text] [PDF]
|
|