Differential connexin distribution accommodates cardiac function in different species

Kempen, Marjan J. A. van; Velde, I. Ten; Wessels, Andy; Oosthoek, P. W.; Gros, Daniël; Jongsma, Habo J.; Moorman, A. F. M.; Lamers, W. H.

doi:10.1002/jemt.1070310511

Cited by 116 publications

(78 citation statements)

References 27 publications

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“…In the atrioventricular bundle, as well as in the atrioventricular node, atrioventricular canal, and lower interatrial septum, they measured low conduction velocities compared with the velocities in the atrial auricle and ventricle. In line with this, the gap junctional proteins Cx40 and Cx43 are generally found to be absent from the atrioventricular bundle and proximal part of the bundle branches in fetal and neonatal mammalian hearts (311). In adult hearts of both mouse and human, the atrioventricular bundle is fast conducting (128,161).…”

Section: E Fate Of the Primary Ringmentioning

confidence: 66%

Cardiac Chamber Formation: Development, Genes, and Evolution

Moorman

Christoffels

2003

Physiological Reviews

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Moorman, Antoon F. M., and Vincent M. Christoffels. Cardiac Chamber Formation: Development, Genes, and Evolution. Physiol Rev 83: 1223-1267, 2003; 10.1152/physrev.00006.2003.—Concepts of cardiac development have greatly influenced the description of the formation of the four-chambered vertebrate heart. Traditionally, the embryonic tubular heart is considered to be a composite of serially arranged segments representing adult cardiac compartments. Conversion of such a serial arrangement into the parallel arrangement of the mammalian heart is difficult to understand. Logical integration of the development of the cardiac conduction system into the serial concept has remained puzzling as well. Therefore, the current description needed reconsideration, and we decided to evaluate the essentialities of cardiac design, its evolutionary and embryonic development, and the molecular pathways recruited to make the four-chambered mammalian heart. The three principal notions taken into consideration are as follows. 1) Both the ancestor chordate heart and the embryonic tubular heart of higher vertebrates consist of poorly developed and poorly coupled “pacemaker-like” cardiac muscle cells with the highest pacemaker activity at the venous pole, causing unidirectional peristaltic contraction waves. 2) From this heart tube, ventricular chambers differentiate ventrally and atrial chambers dorsally. The developing chambers display high proliferative activity and consist of structurally well-developed and well-coupled muscle cells with low pacemaker activity, which permits fast conduction of the impulse and efficacious contraction. The forming chambers remain flanked by slowly proliferating pacemaker-like myocardium that is temporally prevented from differentiating into chamber myocardium. 3) The trabecular myocardium proliferates slowly, consists of structurally poorly developed, but well-coupled, cells and contributes to the ventricular conduction system. The atrial and ventricular chambers of the formed heart are activated and interconnected by derivatives of embryonic myocardium. The topographical arrangement of the distinct cardiac muscle cells in the forming heart explains the embryonic electrocardiogram (ECG), does not require the invention of nodes, and allows a logical transition from a peristaltic tubular heart to a synchronously contracting four-chambered heart. This view on the development of cardiac design unfolds fascinating possibilities for future research.

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Section: E Fate Of the Primary Ringmentioning

confidence: 66%

Cardiac Chamber Formation: Development, Genes, and Evolution

Moorman

Christoffels

2003

Physiological Reviews

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650

526

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“…Previous reports described CX40 as a marker of the proximal ventricular conduction system (VCS) in several mammalian species (Gourdie et al, 1993;Gros et al, 1994Van Kempen et al, 1995). In adult mouse and rat hearts CX40 was shown to be expressed in the His bundle and the bundle branches (Gros et al, 1994.…”

Section: Distribution Of Cx40 In the Conduction Systemmentioning

confidence: 98%

“…In addition, in the adult rat and mouse, CX43 is also absent from the ventricular conduction tissue, i.e., the His bundle and the proximal part of the bundle branches (Van Kempen et al, 1991;Gourdie et al, 1992). Interestingly, CX40 distribution studies (Gourdie et al, 1993;Gros et al, 1994Gros et al, , 1995Van Kempen et al, 1995) showed that CX40 has a more restricted distribution than CX43 in adult mammalian hearts. These authors demonstrated that (2x40 is expressed not only in atria (depending on the species) but also in ventricular conduction system myocytes.…”

mentioning

confidence: 99%

Developmental regulation of connexin 40 gene expression in mouse heart correlates with the differentiation of the conduction system

Delorme

Dahl

Jarry-Guichard

et al. 1995

Developmental Dynamics

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In adult mouse heart, CX40 is expressed in the atria and the proximal part of the ventricular conduction system (the His bundle and the upper parts of the bundle branches). This cardiac tissue is specialized in the conduction of the electrical impulse. CX40 is the only mouse connexin known to be expressed in these parts of the adult conductive tissue and is thus considered as a marker of the conduction system. In the present report, we investigated CX40 expression and distribution during mouse heart development. We first demonstrate that CX40 mRNA is regulated throughout development, as are other heart connexin transcripts, i.e., CX37, CX43, and (2x45, with a decreasing abundance as development proceeds. We also show that the CX40 transcript and protein are similarly regulated, CX40 being expressed as two different phosphorylated and un-phosphorylated forms of 41 and 40 kDa, respectively. Surprisingly, distribution studies demonstrated that CX40 is widely expressed in 11 days post-coitum (dpc) embryonic heart, where it is detected in both the atria and ventricle primordia. As development proceeds, the CX40 distribution pattern in the atria is maintained, whereas a more dynamic pattern is observed in the ventricles. From 14 dpc onwards, as the adult ventricular conduction system differentiates, CX40 decreases in the trabecular network and it is preferentially distributed in the ventricular conduction system. CX40 is thus the marker of the early differentiating conduction system. It is hypothesized that the conduction system is present in unorganized "embryonic" form at 11 dpc and trans-differentiates by 14 dpc into the adult conduction system. 0 1995 Wiley-Liss, Inc.

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“…[1][2][3][4][5][6][7][8][9][10] The structure of the specific conduction system in the right and left septal wall of the human 11 and dog heart 12 is similar to that of the mouse. 13 The generation of connexin knockout mice has revealed the importance of the respective gap junction isoforms for propagation of the electrical impulse through the conduction system.…”

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confidence: 99%

Discontinuous Conduction in Mouse Bundle Branches Is Caused by Bundle-Branch Architecture

et al. 2005

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Background-Recordings of the electrical activity of mouse bundle branches (BBs) suggest reduced conduction velocity (CV) in the midseptal compared with the proximal part of the BB. The present study was performed to elucidate the mechanism responsible for this slowing of conduction. Methods and Results-Hearts of 16 mice were isolated and Langendorff perfused. After the right and left ventricular free walls were removed, the extracellular activity of the BB was mapped with a 247-point electrode. Premature stimulation was used to estimate CV restitution in the BBs. Expression/distribution of connexin40 (Cx40), Cx43, and Cx45 was determined. Morphology of the conduction system was assessed by whole-mount acetylcholine esterase staining and in Cx40 ϩ/KI-GFP hearts. Effective CV in the midseptal part of the left and right BBs was reduced by 50% compared with the proximal BB. CV restitution in the proximal and midseptal parts of the BBs was similar. Myocytes labeled positive for Cx40 and Cx45 in the entire BB. Cx43 colocalized with Cx40 and Cx45 only in the very distal BB. Subcellular distribution of gap junctions differed between proximal and distal BBs. Geometry of the midseptal and distal BBs revealed on both sides a profuse network of interlacing fibers, whereas the proximal BB consisted of a single (right BB) or multiple (left BB) parallel fibers. Conclusions-Comparison of connexin expression/distribution, geometry of the BBs, and CV characteristics suggests that increased path length for activation resulting from BB geometry is responsible for the apparently reduced CV in the midseptal BB of the mouse heart. (Circulation. 2005;112:2235-2244.)

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Differential connexin distribution accommodates cardiac function in different species

Cited by 116 publications

References 27 publications

Cardiac Chamber Formation: Development, Genes, and Evolution

Cardiac Chamber Formation: Development, Genes, and Evolution

Developmental regulation of connexin 40 gene expression in mouse heart correlates with the differentiation of the conduction system

Discontinuous Conduction in Mouse Bundle Branches Is Caused by Bundle-Branch Architecture

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