Connexin45, a Major Connexin of the Rabbit Sinoatrial Node, Is Co-expressed with Connexin43 in a Restricted Zone at the Nodal-Crista Terminalis Border

Abstract

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 nodal-crista 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.

Ageing-dependent remodelling of ion channel and Ca2+clock genes underlying sino-atrial node pacemaking

“…This is in agreement with data obtained from the mouse SAN by Verhijck et al (2001) and Miquerol et al (2004). However, Kwong et al (1998) and Coppen et al (1999) reported that Cx40 protein is widely distributed in the SAN of dogs and rabbits, respectively. Therefore, expression of Cx40 in the SAN may vary among species.…”

Gradient Model Versus Mosaic Model of the Sinoatrial Node

“…15,16 There may be a gradient in coupling in the SA node: in the periphery of the SA node, g j may be higher than in the center. 17,18 Figure 3 shows that even in this case (peripheral lattice with high g j and central lattice with low g j ), the mosaic model cannot explain the difference in cycle length between peripheral and central tissue. The mosaic model is based on the assumptions that there are a substantial number of atrial cells in the SA node and that the properties of SA node cells are uniform.…”

“…The mosaic model is based on the assumptions that there are a substantial number of atrial cells in the SA node and that the properties of SA node cells are uniform. These assumptions may not be valid, however, because (1) atrial muscle abuts the SA node but is not connected to it, 18 and it is important to remove this atrial muscle when isolating cells, and (2) in the study of Wilders et al, 5 in which no relationship was found between electrical activity and cell size, "single" SA node cells with a capacitance (measure of cell size) Ͼ115 pF are included. Such high values indicate cell clusters and invalidate any conclusion.…”

Connexin-Mediated Cardiac Impulse Propagation: Connexin 30.2 Slows Atrioventricular Conduction in Mouse Heart

“…Expression patterns of all cardiac Cxs are shown in Figure 1. Cx43, the major Cx forming GJ channels between working cardiomyocytes of atria and ventricles, is also expressed in the network of Purkinje fibers forming the distal part of the ventricular conduction system (Beyer et al 1989, Gourdie et al 1993, Coppen et al 1999a). Cx40 colocalizes with Cx43 in the atrial working myocytes and is abundantly expressed in the His bundle, bundle branches, and subendocardial network of Purkinje fibers, that is, structures with high conduction velocities.…”