© 2001 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
High resolution optical mapping reveals conduction slowing in connexin43 deficient mice
aThe Heart and Vascular Research Center and the Department of Biomedical Engineering, MetroHealth Campus, Case Western Reserve University, 2500 MetroHealth Drive, Hamman 322, Cleveland, OH 44109-1998, USA
bThe Departments of Medicine, Pediatrics, Surgery and Pathology, and the Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, MO, USA
* Corresponding author. Tel.: +1-216-778-2005; fax: 1-216-778-4924 drosenbaum{at}metrohealth.org
Analysis of mice with genetically altered expression of cardiac connexins can provide insights into the role of individual gap junction channel proteins in cell-to-cell communication, impulse propagation, and arrhythmias. However, conflicting results have been reported regarding conduction velocity slowing in mice heterozygous for a null mutation in the gene encoding connexin43 (Cx43). Methods: High-resolution optical mapping was used to record action potentials from 256 sites, simultaneously, on the ventricular surface of Langendorff perfused hearts from 15 heterozygous (Cx43+/–) and 8 wildtype (Cx43+/+) mice (controls). A sensitive method for measuring epicardial conduction velocity was developed to minimize confounding influences of subepicardial breakthrough and virtual electrode effects. Results: Epicardial conduction velocity was significantly slower (23 to 35%, P<0.01) in Cx43+/– mice compared to wildtype. There was no change in conduction patterns or anisotropic ratio (Cx43+/– 1.54±0.33; Cx43+/+ 1.57±0.17) suggesting that Cx43 expression was reduced uniformly throughout myocardium. The magnitude of reductions in conduction velocity and Cx43 protein expression (45%) were similar in mice in which the null allele occurred in a pure C57BL/6J genetic background versus a mixed (C57BL/6J X 129) background. Action potential duration did not differ between mice of different genotypes. Conclusions: A
50% reduction of Cx43 expression causes significant conduction velocity slowing in the Cx43+/– mouse heart. The apparent lack of conduction velocity changes reported in previous studies may be related to technical factors rather than variations in genetic background. High-resolution optical mapping is a powerful tool for investigating molecular determinants of propagation and arrhythmias in genetically engineered mice.
KEYWORDS Cell communication; Gap junctions; Gene expression; Mapping
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
A. Maguy, S. Le Bouter, P. Comtois, D. Chartier, L. Villeneuve, R. Wakili, K. Nishida, and S. Nattel Ion Channel Subunit Expression Changes in Cardiac Purkinje Fibers: A Potential Role in Conduction Abnormalities Associated With Congestive Heart Failure Circ. Res., May 8, 2009; 104(9): 1113 - 1122. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Kontogeorgis, X. Li, E. Y. Kang, J. E. Feig, M. Ponzio, G. Kang, R. A. Kaba, A. L. Wit, E. A. Fisher, G. E. Morley, et al. Decreased connexin43 expression in the mouse heart potentiates pacing-induced remodeling of repolarizing currents Am J Physiol Heart Circ Physiol, November 1, 2008; 295(5): H1905 - H1916. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. W. Mills, S. M. Narayan, and A. D. McCulloch Mechanisms of conduction slowing during myocardial stretch by ventricular volume loading in the rabbit Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1270 - H1278. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Sato, T. Ohkusa, H. Honjo, S. Suzuki, M.-a. Yoshida, Y. S. Ishiguro, H. Nakagawa, M. Yamazaki, M. Yano, I. Kodama, et al. Altered expression of connexin43 contributes to the arrhythmogenic substrate during the development of heart failure in cardiomyopathic hamster Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1164 - H1173. [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] |
||||
![]() |
H. V.M. van Rijen and J. M.T. de Bakker Penetrance of monogenetic cardiac conduction diseases. A matter of conduction reserve? Cardiovasc Res, December 1, 2007; 76(3): 379 - 380. [Full Text] [PDF] |
||||
![]() |
F. G. Akar, R. D. Nass, S. Hahn, E. Cingolani, M. Shah, G. G. Hesketh, D. DiSilvestre, R. S. Tunin, D. A. Kass, and G. F. Tomaselli Dynamic changes in conduction velocity and gap junction properties during development of pacing-induced heart failure Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H1223 - H1230. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. E. Sawaya, Y. S. Rajawat, T. G. Rami, G. Szalai, R. L. Price, N. Sivasubramanian, D. L. Mann, and D. S. Khoury Downregulation of connexin40 and increased prevalence of atrial arrhythmias in transgenic mice with cardiac-restricted overexpression of tumor necrosis factor Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1561 - H1567. [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] |
||||
![]() |
J. Li, V. V. Patel, and G. L. Radice Dysregulation of cell adhesion proteins and cardiac arrhythmogenesis. Clin. Med. Res., March 1, 2006; 4(1): 42 - 52. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. R. Mills, N. Mal, F. Forudi, Z. B. Popovic, M. S. Penn, and K. R. Laurita Optical mapping of late myocardial infarction in rats Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1298 - H1306. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Betsuyaku, N. S. Nnebe, R. Sundset, S. Patibandla, C. M. Krueger, and K. A. Yamada Overexpression of cardiac connexin45 increases susceptibility to ventricular tachyarrhythmias in vivo Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H163 - H171. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. J. Gard, K. Yamada, K. G. Green, B. C. Eloff, D. S. Rosenbaum, X. Wang, J. Robbins, R. B. Schuessler, K. A. Yamada, and J. E. Saffitz Remodeling of gap junctions and slow conduction in a mouse model of desmin-related cardiomyopathy Cardiovasc Res, August 15, 2005; 67(3): 539 - 547. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. J. Hyatt, S. F. Mironov, F. J. Vetter, C. W. Zemlin, and A. M. Pertsov Optical Action Potential Upstroke Morphology Reveals Near-Surface Transmural Propagation Direction Circ. Res., August 5, 2005; 97(3): 277 - 284. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. V.M. van Rijen, J. M.T. de Bakker, and T. A.B. van Veen Hypoxia, electrical uncoupling, and conduction slowing: Role of conduction reserve Cardiovasc Res, April 1, 2005; 66(1): 9 - 11. [Full Text] [PDF] |
||||
![]() |
N. Zeevi-Levin, Y. D. Barac, Y. Reisner, I. Reiter, G. Yaniv, G. Meiry, Z. Abassi, S. Kostin, J. Schaper, M. R. Rosen, et al. Gap junctional remodeling by hypoxia in cultured neonatal rat ventricular myocytes Cardiovasc Res, April 1, 2005; 66(1): 64 - 73. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. A Jones, M. K Lancaster, and M. R Boyett Ageing-related changes of connexins and conduction within the sinoatrial node J. Physiol., October 15, 2004; 560(2): 429 - 437. [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] |
||||
![]() |
B. London Staying Connected Without Connexin43: Can You Hear Me Now? Circ. Res., July 23, 2004; 95(2): 120 - 121. [Full Text] [PDF] |
||||
![]() |
P. Beauchamp, C. Choby, T. Desplantez, K. de Peyer, K. Green, K. A. Yamada, R. Weingart, J. E. Saffitz, and A. G. Kleber Electrical Propagation in Synthetic Ventricular Myocyte Strands From Germline Connexin43 Knockout Mice Circ. Res., July 23, 2004; 95(2): 170 - 178. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. R. Efimov, V. P. Nikolski, and G. Salama Optical Imaging of the Heart Circ. Res., July 9, 2004; 95(1): 21 - 33. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Libbus, X. Wan, and D. S. Rosenbaum Electrotonic load triggers remodeling of repolarizing current Ito in ventricle Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1901 - H1909. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Gros, L. Dupays, S. Alcolea, S. Meysen, L. Miquerol, and M. Theveniau-Ruissy Genetically modified mice: tools to decode the functions of connexins in the heart--new models for cardiovascular research Cardiovasc Res, May 1, 2004; 62(2): 299 - 308. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. R de Groot and R. Coronel Acute ischemia-induced gap junctional uncoupling and arrhythmogenesis Cardiovasc Res, May 1, 2004; 62(2): 323 - 334. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. G. Petrich, B. C. Eloff, D. L. Lerner, A. Kovacs, J. E. Saffitz, D. S. Rosenbaum, and Y. Wang Targeted Activation of c-Jun N-terminal Kinase in Vivo Induces Restrictive Cardiomyopathy and Conduction Defects J. Biol. Chem., April 9, 2004; 279(15): 15330 - 15338. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. E. Saffitz and A. G. Kleber Effects of Mechanical Forces and Mediators of Hypertrophy on Remodeling of Gap Junctions in the Heart Circ. Res., March 19, 2004; 94(5): 585 - 591. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. V.M. van Rijen, D. Eckardt, J. Degen, M. Theis, T. Ott, K. Willecke, H. J. Jongsma, T. Opthof, and J. M.T. de Bakker Slow Conduction and Enhanced Anisotropy Increase the Propensity for Ventricular Tachyarrhythmias in Adult Mice With Induced Deletion of Connexin43 Circulation, March 2, 2004; 109(8): 1048 - 1055. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. C. Eloff, E. Gilat, X. Wan, and D. S. Rosenbaum Pharmacological Modulation of Cardiac Gap Junctions to Enhance Cardiac Conduction: Evidence Supporting a Novel Target for Antiarrhythmic Therapy Circulation, December 23, 2003; 108(25): 3157 - 3163. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. T. Maguire, H. Wakimoto, V. V. Patel, P. E. Hammer, K. Gauvreau, and C. I. Berul Implications of ventricular arrhythmia vulnerability during murine electrophysiology studies Physiol Genomics, September 29, 2003; 15(1): 84 - 91. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. P. Thomas, J. P. Kucera, L. Bircher-Lehmann, Y. Rudy, J. E. Saffitz, and A. G. Kleber Impulse Propagation in Synthetic Strands of Neonatal Cardiac Myocytes With Genetically Reduced Levels of Connexin43 Circ. Res., June 13, 2003; 92(11): 1209 - 1216. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. E. I. Gittens, A. A. Mhawi, D. Lidington, Y. Ouellette, and G. M. Kidder Functional analysis of gap junctions in ovarian granulosa cells: distinct role for connexin43 in early stages of folliculogenesis Am J Physiol Cell Physiol, April 1, 2003; 284(4): C880 - C887. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Kanno, A. Kovacs, K. A. Yamada, and J. E. Saffitz Connexin43 as a determinant of myocardial infarct size following coronary occlusion in mice J. Am. Coll. Cardiol., February 19, 2003; 41(4): 681 - 686. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. P. Kucera, S. Rohr, and Y. Rudy Localization of Sodium Channels in Intercalated Disks Modulates Cardiac Conduction Circ. Res., December 13, 2002; 91(12): 1176 - 1182. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. A. Papadatos, P. M. R. Wallerstein, C. E. G. Head, R. Ratcliff, P. A. Brady, K. Benndorf, R. C. Saumarez, A. E. O. Trezise, C. L.-H. Huang, J. I. Vandenberg, et al. From the Cover: Slowed conduction and ventricular tachycardia after targeted disruption of the cardiac sodium channel gene Scn5a PNAS, April 30, 2002; 99(9): 6210 - 6215. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. M. Johnson, E. M. Kanter, K. G. Green, J. G. Laing, T. Betsuyaku, E. C. Beyer, T. H. Steinberg, J. E. Saffitz, and K. A. Yamada Redistribution of connexin45 in gap junctions of connexin43-deficient hearts Cardiovasc Res, March 1, 2002; 53(4): 921 - 935. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. A Eisenberg and L. M Eisenberg Measuring electrophysiological changes in transgenic mouse models of cardiovascular disease Cardiovasc Res, September 1, 2001; 51(4): 630 - 632. [Full Text] [PDF] |
||||
![]() |
G. A. Papadatos, P. M. R. Wallerstein, C. E. G. Head, R. Ratcliff, P. A. Brady, K. Benndorf, R. C. Saumarez, A. E. O. Trezise, C. L.-H. Huang, J. I. Vandenberg, et al. From the Cover: Slowed conduction and ventricular tachycardia after targeted disruption of the cardiac sodium channel gene Scn5a PNAS, April 30, 2002; 99(9): 6210 - 6215. [Abstract] [Full Text] [PDF] |
||||










