(Circulation. 2001;103:1591.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Impaired Conduction in the Bundle Branches of Mouse Hearts Lacking the Gap Junction Protein Connexin40
From the Department of Medical Physiology (H.V.M.v.R., T.A.B.v.V., M.J.A.v.K., T.O., H.J.J.), Utrecht, The Netherlands; Interuniversity Cardiology Institute of the Netherlands (F.J.G.W.-S., J.M.T.d.B.), Utrecht, The Netherlands; the Department of Medical Physics (M.P.), Academic Medical Center, Amsterdam, The Netherlands; the Institute of Genetics (O.K., K.W.), University of Bonn, Germany; and the Department of Cardiology (J.M.T.d.B.), University Medical Center, Utrecht, The Netherlands.
Correspondence to Harold V.M. van Rijen, PhD, Department of Medical Physiology, Faculty of Medicine, University of Utrecht, PO Box 80043, 3508 TA Utrecht, The Netherlands. E-mail H.V.M.vanRijen{at}med.uu.nl
Background—Connexin (Cx)40 and Cx45 are the major protein subunits of gap junction channels in the conduction system of mammals. To determine the role of Cx40, we correlated cardiac activation with Connexin distribution in normal and Cx40-deficient mice hearts.
Methods and Results—Epicardial and septal activation was recorded in Langendorff-perfused adult mice hearts with a 247-point compound electrode (interelectrode distance, 0.3 mm). After electrophysiological measurements, hearts were prepared for immunohistochemistry and histology to determine Connexin distribution and fibrosis. In both wild-type and Cx40-deficient animals, epicardial activation patterns were similar. The right and left ventricular septum was invariably activated from base to apex. Histology revealed a continuity of myocytes from the common bundle to the septal myocardium. Within this continuity, colocalization was found of Cx43 and Cx45 but not of Cx40 and Cx43. Both animals showed similar His-bundle activation. In Cx40-deficient mice, the proximal bundle branches expressed Cx45 only. The absence of Cx40 in the proximal bundles correlated with right bundle-branch block. Conduction in the left bundle branch was impaired as compared with wild-type animals.
Conclusions—Our data show that (1) in mice, a continuity exists between the common bundle and the septum, and (2) Cx40 deficiency results in right bundle-branch block and impaired left bundle-branch conduction.
Key Words: proteins • bundle-branch block • conduction • immunohistochemistry • mapping
This article has been cited by other articles:
 |
|
 |
|
  R. Klocke, W. Tian, M. T. Kuhlmann, and S. Nikol Surgical animal models of heart failure related to coronary heart disease Cardiovasc Res, April 1, 2007; 74(1): 29 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rackauskas, M. M. Kreuzberg, M. Pranevicius, K. Willecke, V. K. Verselis, and F. F. Bukauskas Gating Properties of Heterotypic Gap Junction Channels Formed of Connexins 40, 43, and 45 Biophys. J., March 15, 2007; 92(6): 1952 - 1965. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. F. Bukauskas, M. M. Kreuzberg, M. Rackauskas, A. Bukauskiene, M. V. L. Bennett, V. K. Verselis, and K. Willecke Properties of mouse connexin 30.2 and human connexin 31.9 hemichannels: Implications for atrioventricular conduction in the heart PNAS, June 20, 2006; 103(25): 9726 - 9731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Kreuzberg, J. W. Schrickel, A. Ghanem, J.-S. Kim, J. Degen, U. Janssen-Bienhold, T. Lewalter, K. Tiemann, and K. Willecke Connexin30.2 containing gap junction channels decelerate impulse propagation through the atrioventricular node PNAS, April 11, 2006; 103(15): 5959 - 5964. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ozawa, Y. K. Hayashi, M. Ogawa, R. Kurokawa, H. Matsumoto, S. Noguchi, I. Nonaka, and I. Nishino Emerin-Lacking Mice Show Minimal Motor and Cardiac Dysfunctions with Nuclear-Associated Vacuoles Am. J. Pathol., March 1, 2006; 168(3): 907 - 917. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A.B. van Veen, H. V.M. van Rijen, M. J.A. van Kempen, L. Miquerol, T. Opthof, D. Gros, M. A. Vos, H. J. Jongsma, and J. M.T. de Bakker Discontinuous Conduction in Mouse Bundle Branches Is Caused by Bundle-Branch Architecture Circulation, October 11, 2005; 112(15): 2235 - 2244. [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]
|
|
|
|
|
|
T. A.B. van Veen, M. Stein, A. Royer, K. Le Quang, F. Charpentier, W. H. Colledge, C. L.-H. Huang, R. Wilders, A. A. Grace, D. Escande, et al. Impaired Impulse Propagation in Scn5a-Knockout Mice: Combined Contribution of Excitability, Connexin Expression, and Tissue Architecture in Relation to Aging Circulation, September 27, 2005; 112(13): 1927 - 1935. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Kreuzberg, G. Sohl, J.-S. Kim, V. K. Verselis, K. Willecke, and F. F. Bukauskas Functional Properties of Mouse Connexin30.2 Expressed in the Conduction System of the Heart Circ. Res., June 10, 2005; 96(11): 1169 - 1177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Royer, T. A.B. van Veen, S. Le Bouter, C. Marionneau, V. Griol-Charhbili, A.-L. Leoni, M. Steenman, H. V.M. van Rijen, S. Demolombe, C. A. Goddard, et al. Mouse Model of SCN5A-Linked Hereditary Lenegre's Disease: Age-Related Conduction Slowing and Myocardial Fibrosis Circulation, April 12, 2005; 111(14): 1738 - 1746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Khan Identifying and understanding the role of pulmonary vein activity in atrial fibrillation Cardiovasc Res, December 1, 2004; 64(3): 387 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. E.J. Teunissen, H. J. Jongsma, and M. F.A. Bierhuizen Regulation of myocardial connexins during hypertrophic remodelling Eur. Heart J., November 2, 2004; 25(22): 1979 - 1989. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. P. G. Moskowitz, A. Pizard, V. V. Patel, B. G. Bruneau, J. B. Kim, S. Kupershmidt, D. Roden, C. I. Berul, C. E. Seidman, and J. G. Seidman The T-Box transcription factor Tbx5 is required for the patterning and maturation of the murine cardiac conduction system Development, August 15, 2004; 131(16): 4107 - 4116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Miquerol, S. Meysen, M. Mangoni, P. Bois, H. V.M van Rijen, P. Abran, H. Jongsma, J. Nargeot, and D. Gros Architectural and functional asymmetry of the His-Purkinje system of the murine heart Cardiovasc Res, July 1, 2004; 63(1): 77 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. E.J Teunissen and M. F.A Bierhuizen Transcriptional control of myocardial connexins Cardiovasc Res, May 1, 2004; 62(2): 246 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P Moreno Biophysical properties of homomeric and heteromultimeric channels formed by cardiac connexins Cardiovasc Res, May 1, 2004; 62(2): 276 - 286. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
S. M. Taffet and J. Jalife Swapping Connexin Genes: How Big Is the Gap? Circ. Res., January 9, 2004; 94(1): 4 - 6. [Full Text] [PDF]
|
|
|
|
|
|
S. Alcolea, T. Jarry-Guichard, J. de Bakker, D. Gonzalez, W. Lamers, S. Coppen, L. Barrio, H. Jongsma, D. Gros, and H. van Rijen Replacement of Connexin40 by Connexin45 in the Mouse: Impact on Cardiac Electrical Conduction Circ. Res., January 9, 2004; 94(1): 100 - 109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. SAEZ, V. M. BERTHOUD, M. C. BRANES, A. D. MARTINEZ, and E. C. BEYER Plasma Membrane Channels Formed by Connexins: Their Regulation and Functions Physiol Rev, October 1, 2003; 83(4): 1359 - 1400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Gu, F. C. Smith, S. M. Taffet, and M. Delmar High Incidence of Cardiac Malformations in Connexin40-Deficient Mice Circ. Res., August 8, 2003; 93(3): 201 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. de Wit, F. Roos, S.-S. Bolz, and U. Pohl Lack of vascular connexin 40 is associated with hypertension and irregular arteriolar vasomotion Physiol Genomics, April 16, 2003; 13(2): 169 - 177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. F. Bukauskas, A. Bukauskiene, V. K. Verselis, and M. V. L. Bennett Coupling asymmetry of heterotypic connexin 45/ connexin 43-EGFP gap junctions: Properties of fast and slow gating mechanisms PNAS, May 14, 2002; 99(10): 7113 - 7118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M.W van der Velden and H. J Jongsma Cardiac gap junctions and connexins: their role in atrial fibrillation and potential as therapeutic targets Cardiovasc Res, May 1, 2002; 54(2): 270 - 279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Olgin and S. Verheule Transgenic and knockout mouse models of atrial arrhythmias Cardiovasc Res, May 1, 2002; 54(2): 280 - 286. [Abstract] [Full Text] [PDF]
|
|