Published online before print September 18, 2003, doi: 10.1161/01.RES.0000095977.66660.86
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2003 American Heart Association, Inc.
Cellular Biology |
Cell Coupling Between Ventricular Myocyte Pairs From Connexin43-Deficient Murine Hearts
From the Department of Pharmacology and Center for Molecular Therapeutics (J.-A.Y., A.L.W.), College of Physicians and Surgeons, Columbia University, New York, NY; The Leon H. Charney Division of Cardiology, Department of Medicine (D.E.G., F.L., G.I.F.), New York University School of Medicine, New York, NY.
Correspondence to Andrew L. Wit, PhD, Department of Pharmacology, College of Physicians and Surgeons of Columbia University, 630 W 168th St, New York, NY 10032. E-mail alw4{at}columbia.edu
Mice with cardiac-restricted inactivation of the connexin43 gene (CKO mice) have moderate slowing of ventricular conduction and lethal arrhythmias. Mechanisms through which propagation is maintained in the absence of Cx43 are unknown. We evaluated gap junctional conductance in CKO ventricular pairs using dual patch clamp methods. Junctional coupling was reduced to 4±2 nS (side-to-side) and 11±2 nS (end-to-end), including 21% of cell-pairs with no detectable coupling, compared with 588±104 nS (side-to-side) and 558±92 nS (end-to-end) in control cell-pairs. Voltage dependence of control gap junctions was characteristic of Cx43. CKO conductance showed increased voltage dependence, suggesting low-level expression of other connexin isoforms. From theoretical models, this degree of CKO coupling is not expected to support levels of conduction persisting in vivo, suggesting the possibility that there are additional mechanisms for maintained propagation when gap junctional conductance is severely reduced.
Key Words: gap junctions • connexin • remodeling • arrhythmias
This article has been cited by other articles:
 |
|
 |
|
  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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 R. Squecco, C. Sassoli, F. Nuti, M. Martinesi, F. Chellini, D. Nosi, S. Zecchi-Orlandini, F. Francini, L. Formigli, and E. Meacci Sphingosine 1-Phosphate Induces Myoblast Differentiation through Cx43 Protein Expression: A Role for a Gap Junction-dependent and -independent Function Mol. Biol. Cell, November 1, 2006; 17(11): 4896 - 4910. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Pollard and R. C. Barr Cardiac microimpedance measurement in two-dimensional models using multisite interstitial stimulation Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1976 - H1987. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Tong, J. E. I. Gittens, G. M. Kidder, and D. Bai Patch-clamp study reveals that the importance of connexin43-mediated gap junctional communication for ovarian folliculogenesis is strain specific in the mouse Am J Physiol Cell Physiol, January 1, 2006; 290(1): C290 - C297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ando, R. G. Katare, Y. Kakinuma, D. Zhang, F. Yamasaki, K. Muramoto, and T. Sato Efferent Vagal Nerve Stimulation Protects Heart Against Ischemia-Induced Arrhythmias by Preserving Connexin43 Protein Circulation, July 12, 2005; 112(2): 164 - 170. [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]
|
|
|
|
 |
|
 D. A. Iacobas, S. Iacobas, W. E. I. Li, G. Zoidl, R. Dermietzel, and D. C. Spray Genes controlling multiple functional pathways are transcriptionally regulated in connexin43 null mouse heart Physiol Genomics, February 10, 2005; 20(3): 211 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Danik, F. Liu, J. Zhang, H. J. Suk, G. E. Morley, G. I. Fishman, and D. E. Gutstein Modulation of Cardiac Gap Junction Expression and Arrhythmic Susceptibility Circ. Res., November 12, 2004; 95(10): 1035 - 1041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Swietach and R. D. Vaughan-Jones Novel method for measuring junctional proton permeation in isolated ventricular myocyte cell pairs Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2352 - H2363. [Abstract] [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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
R. Schulz and G. Heusch Connexin 43 and ischemic preconditioning Cardiovasc Res, May 1, 2004; 62(2): 335 - 344. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J Vink, S. O Suadicani, D. M Vieira, M. Urban-Maldonado, Y. Gao, G. I Fishman, and D. C Spray Alterations of intercellular communication in neonatal cardiac myocytes from connexin43 null mice Cardiovasc Res, May 1, 2004; 62(2): 397 - 406. [Abstract] [Full Text] [PDF]
|
|