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Journal of Histochemistry and Cytochemistry, Vol. 47, 907-918, July 1999, Copyright © 1999, The Histochemical Society, Inc.
Connexin45, a Major Connexin of the Rabbit Sinoatrial Node, Is Co-expressed with Connexin43 in a Restricted Zone at the NodalCrista Terminalis Border
Steven R. Coppena,
Itsuo Kodamab,
Mark R. Boyettc,
Halina Dobrzynskic,
Yoshiko Takagishib,
Haruo Honjob,
Hung-I Yeha,d, and
Nicholas J. Seversa
a National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom
b Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan
c Department of Physiology, University of Leeds, Leeds, United Kingdom
d Mackay Memorial Hospital, Taipei Medical College, Taipai, Taiwan
Correspondence to:
Nicholas J. Severs, Cardiac Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK.
The pacemaker of the heart, the sinoatrial (SA) node, is characterized by unique electrical coupling properties. To investigate the contribution of gap junction organization and composition to these properties, the spatial pattern of expression of three gap junctional proteins, connexin45 (Cx45), connexin40 (Cx40), and connexin43 (Cx43), was investigated by immunocytochemistry combined with confocal microscopy. The SA nodal regions of rabbits were dissected and rapidly frozen. Serial cryosections were double labeled for Cx45 and Cx43 and for Cx40 and Cx43, using pairs of antibody probes raised in different species. Dual-channel scanning confocal microscopy was applied to allow simultaneous visualization of the different connexins. Cx45 and Cx40, but not Cx43, were expressed in the central SA node. The major part of the SA nodalcrista terminalis border revealed a sharply demarcated boundary between Cx43-expressing myocytes of the crista terminalis and Cx45/Cx40-expressing myocytes of the node. On the endocardial side, however, a transitional zone between the crista terminalis and the periphery of the node was detected in which Cx43 and Cx45 expression merged. These distinct patterns of connexin compartmentation and merger identified suggest a morphological basis for minimization of contact between the tissues, thereby restricting the hyperpolarizing influence of the atrial muscle on the SA node while maintaining a communication route for directed exit of the impulse into the crista terminalis. (J Histochem Cytochem 47:907918, 1999)
Key Words:
gap junctions, connexins, heart, sinoatrial node, confocal microscopy

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|
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|

|
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|
 |
|

|
 |

|
 |
 
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55(4):
727 - 738.
[Abstract]
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|
 |
|

|
 |

|
 |
 
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Circ. Res.,
May 17, 2002;
90(9):
939 - 950.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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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]
|
 |
|

|
 |

|
 |
 
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Heterogeneous Expression of Ca2+ Handling Proteins in Rabbit Sinoatrial Node
J. Histochem. Cytochem.,
March 1, 2002;
50(3):
311 - 324.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Cardiovasc Res,
March 1, 2002;
53(4):
1043 - 1045.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. J.A. van Kempen and E.E. Verheijck
Of antibodies and their interaction
Cardiovasc Res,
March 1, 2002;
53(4):
1046 - 1046.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Honjo, M. R Boyett, S. R Coppen, Y. Takagishi, T. Opthof, N. J Severs, and I. Kodama
Heterogeneous expression of connexins in rabbit sinoatrial node cells: correlation between connexin isotype and cell size
Cardiovasc Res,
January 1, 2002;
53(1):
89 - 96.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Dobrzynski, D. D.R. Marples, H. Musa, T. T. Yamanushi, Z. Henderson, Y. Takagishi, H. Honjo, I. Kodama, and M. R. Boyett
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J. Histochem. Cytochem.,
October 1, 2001;
49(10):
1221 - 1234.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Opthof
Function and structure of the mouse sinus node: nothing you can see that isn't shown
Cardiovasc Res,
October 1, 2001;
52(1):
1 - 4.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E.E. Verheijck, M. J.A. van Kempen, M. Veereschild, J. Lurvink, H. J. Jongsma, and L. N. Bouman
Electrophysiological features of the mouse sinoatrial node in relation to connexin distribution
Cardiovasc Res,
October 1, 2001;
52(1):
40 - 50.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. A.B. van Veen, H. V.M. van Rijen, and T. Opthof
Cardiac gap junction channels: modulation of expression and channel properties
Cardiovasc Res,
August 1, 2001;
51(2):
217 - 229.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Verheule, M. J. A. van Kempen, S. Postma, M. B. Rook, and H. J. Jongsma
Gap junctions in the rabbit sinoatrial node
Am J Physiol Heart Circ Physiol,
May 1, 2001;
280(5):
H2103 - H2115.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Zhang, A. V. Holden, and M. R. Boyett
Gradient Model Versus Mosaic Model of the Sinoatrial Node
Circulation,
January 30, 2001;
103(4):
584 - 588.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M.R. Boyett, H. Honjo, and I. Kodama
The sinoatrial node, a heterogeneous pacemaker structure
Cardiovasc Res,
September 1, 2000;
47(4):
658 - 687.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Zhang, A. V. Holden, I. Kodama, H. Honjo, M. Lei, T. Varghese, and M. R. Boyett
Mathematical models of action potentials in the periphery and center of the rabbit sinoatrial node
Am J Physiol Heart Circ Physiol,
July 1, 2000;
279(1):
H397 - H421.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. J. Jongsma and R. Wilders
Gap Junctions in Cardiovascular Disease
Circ. Res.,
June 23, 2000;
86(12):
1193 - 1197.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Dobrzynski, S. M. Rothery, D. D.R. Marples, S. R. Coppen, Y. Takagishi, H. Honjo, M. M. Tamkun, Z. Henderson, I. Kodama, N. J. Severs, et al.
Presence of the Kv1.5 K+ Channel in the Sinoatrial Node
J. Histochem. Cytochem.,
June 1, 2000;
48(6):
769 - 780.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
W. H Litchenberg, L. W Norman, A. K Holwell, K. L Martin, K. W Hewett, and R. G Gourdie
The rate and anisotropy of impulse propagation in the postnatal terminal crest are correlated with remodeling of Cx43 gap junction pattern
Cardiovasc Res,
January 14, 2000;
45(2):
379 - 387.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Kostin and J. Schaper
Tissue-Specific Patterns of Gap Junctions in Adult Rat Atrial and Ventricular Cardiomyocytes In Vivo and In Vitro
Circ. Res.,
May 11, 2001;
88(9):
933 - 939.
[Abstract]
[Full Text]
[PDF]
|
 |
|
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