Gap Junctional Connexins in the Developing Mouse Cardiac Conduction System

Miquerol, Lucile; Dupays, Laurent; Théveniau-Ruissy, Magali; Alcoléa, Sébastien; Jarry-Guichard, T.; Abran, Patrice; Gros, Daniël

doi:10.1002/0470868066.ch6

Cited by 43 publications

(33 citation statements)

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“…S. SCHULTE ET AL. Miquerol et al 2003). In addition, we have demonstrated that the expression level of Cx45 in the neonatal rat cardiomyocytes examined in our study is very low, whereas levels of Cx40 and Cx43 are much higher, confirming data from previous studies of our group (Salameh et al 2006).…”

supporting

confidence: 91%

Neonatal Rat Cardiomyocytes Show Characteristics of Nonhomotypic Gap Junction Channels

Schulte

Scheffler

Rojas-Gómez

et al. 2008

Cell Communication & Adhesion

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Neonatal rat cardiomyocytes mainly coexpress the connexins Cx40, Cx43, and to a small amount Cx45, leading to potential formation of mixed (heteromeric/heterotypic) gap junction channels. Using the dual-voltage clamp technique with switching clamp circuits, the authors investigated voltage sensitivity of gap junction channels between cell pairs of Cx40, Cx43, and Cx45 stably transfected HeLa cells and compared those data to data obtained from cell pairs of cultured neonatal rat cardiomyocytes. In accordance to previously published data, the relationship between normalized conductance and transjunctional voltage (g/V j ) was quasisymmetrical for the transfected HeLa cells, indicating homotypic gap junction channels. Boltzmann curves fitted to data obtained from neonatal rat cardiomyocyte pairs expressing both Cx40 and Cx43 showed an asymmetrical inactivation pattern, which cannot be explained by the presence of pure populations of homotypic gap junction channels of either isoform. In conclusion the authors assume the additional presence of heterotypic and possibly even heteromeric gap junction channels in neonatal rat cardiomyocytes.

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supporting

confidence: 91%

Neonatal Rat Cardiomyocytes Show Characteristics of Nonhomotypic Gap Junction Channels

Schulte

Scheffler

Rojas-Gómez

et al. 2008

Cell Communication & Adhesion

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“…While the conduction system also expresses connexin 30.2, it appears that it is not sufficient to maintain normal AV conduction. This may be related to its very slow conduction properties (11).…”

Section: Discussionmentioning

confidence: 99%

“…When AV-node function is impaired, there is an abnormal delay in or absence of conduction from the atria to the ventricles. The gap junctions that are found in the cell-to-cell contacts between AV-nodal cells and in the intercalated discs of cardiac myocytes are important for impulse propagation (10,11). There are 4 principal connexins that are found in the gap junctions of the adult heart (connexins 40, 43, 45, and 30.2) (12).…”

Section: Introductionmentioning

confidence: 99%

Coxsackievirus and adenovirus receptor (CAR) mediates atrioventricular-node function and connexin 45 localization in the murine heart

Lim¹,

Xiong²,

Dörner³

et al. 2008

J. Clin. Invest.

131

130

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The coxsackievirus and adenovirus receptor (CAR) is a transmembrane protein that belongs to the family of adhesion molecules. In the postnatal heart, it is localized predominantly at the intercalated disc, where its function is not known. Here, we demonstrate that a first degree or complete block of atrioventricular (AV) conduction developed in the absence of CAR in the adult mouse heart and that prolongation of AV conduction occurred in the embryonic heart of the global CAR-KO mouse. In the cardiac-specific CAR-KO (CAR-cKO) mouse, we observed the loss of connexin 45 localization to the cell-cell junctions of the AV node but preservation of connexin 40 and 43 in contracting myocardial cells and connexin 30.2 in the AV node. There was also a marked decrease in β-catenin and zonula occludens-1 (ZO-1) localization to the intercalated discs of CAR-cKO mouse hearts at 8 weeks before the mice developed cardiomyopathy at 21 weeks of age. We also found that CAR formed a complex with connexin 45 via its PSD-95/DigA/ZO-1-binding (PDZ-binding) motifs. We conclude that CAR expression is required for normal AV-node conduction and cardiac function. Furthermore, localization of connexin 45 at the AV-node cell-cell junction and of β-catenin and ZO-1 at the ventricular intercalated disc are dependent on CAR.

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“…5,6 According to this model, conductive myocytes are nonproliferative and subsequent growth of the conduction system occurs by accretional recruitment of new myocytes (or ingrowth). However, in the chick, a perivascular network of Purkinje fibers is localized deep in the myocardium in proximity to coronary vessels, whereas in the mouse, as in humans, Purkinje fibers are present only at the subendocardial ventricular surface 1,7,8 and it is unclear whether the chick model is applicable to the mammalian VCS. In mammals an outgrowth model has been proposed for development of the central VCS, by which conductive cells develop independently of the working myocardium from a pool of conductive progenitors at the crest of the interventricular septum (IVS) in the early embryonic heart.…”

mentioning

confidence: 99%

Biphasic Development of the Mammalian Ventricular Conduction System

Miquerol

Moreno-Rascon

Beyer

et al. 2010

Circulation Research

105

127

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Rationale: The ventricular conduction system controls the propagation of electric activity through the heart to coordinate cardiac contraction. This system is composed of specialized cardiomyocytes organized in defined structures including central components and a peripheral Purkinje fiber network. How the mammalian ventricular conduction system is established during development remains controversial. Objective: To define the lineage relationship between cells of the murine ventricular conduction system and surrounding working myocytes. Methods and Results: A retrospective clonal analysis using the ␣-cardiac actin nlaacZ/؉ mouse line was carried out in three week old hearts. Clusters of clonally related myocytes were screened for conductive cells using Key Words: conduction system Ⅲ cell lineage Ⅲ clonal analysis Ⅲ nlaacZ Ⅲ Purkinje fibers T he cardiac conduction system controls the generation and propagation of electric activity through the heart to coordinate cardiac contraction. Atrial contraction is initiated by the sinoatrial node or pacemaker. After a delay mediated by the atrioventricular node (AVN), the ventricular conduction system (VCS) ensures rapid propagation of electric activity to the ventricular apex. 1 The VCS is comprised of a central component, the atrioventricular (AV or His) bundle and right and left bundle branches, and a peripheral component composed of a dense ellipsoid network of Purkinje fibers. These structures have been well characterized in adult mouse and human hearts by their specific histological and electrophysiological properties. 2,3 However, despite the clinical importance of the VCS in regulating cardiac rhythm, important questions remain as to the origin and the mode of development of the mammalian VCS. 4 Existing views of VCS development are largely based on data obtained in avian embryos, despite major anatomic differences within the VCS between birds and mammals. In the avian system, lineage analysis using replication defective retroviral labeling has demonstrated that conductive cells share common progenitors with working cardiomyocytes and that the VCS develops by a process of induction and recruitment of myocytes through endothelial derived signals. 5,6 According to this model, conductive myocytes are nonproliferative and subsequent growth of the conduction system occurs by accretional recruitment of new myocytes (or ingrowth). However, in the chick, a perivascular network of Purkinje fibers is localized deep in the myocardium in proximity to coronary vessels, whereas in the mouse, as in humans, Purkinje fibers are present only at the subendocardial ventricular surface 1,7,8 and it is unclear whether the chick model is applicable to the mammalian VCS. In mammals an outgrowth model has been proposed for development of the central VCS, by which conductive cells develop independently of the working myocardium from a pool of conductive Original

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Gap Junctional Connexins in the Developing Mouse Cardiac Conduction System

Cited by 43 publications

References 0 publications

Neonatal Rat Cardiomyocytes Show Characteristics of Nonhomotypic Gap Junction Channels

Neonatal Rat Cardiomyocytes Show Characteristics of Nonhomotypic Gap Junction Channels

Coxsackievirus and adenovirus receptor (CAR) mediates atrioventricular-node function and connexin 45 localization in the murine heart

Biphasic Development of the Mammalian Ventricular Conduction System

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