Distribution of Gap Junctions in the Heart

In the first part of this chapter the distribution of gap junctions within a cell is discussed. In the second part the connexin pattern in the heart is described, and in the third part the expression of various connexins in the vasculature is outlined. 

Heart muscle fibers are coupled by gap junctions. These intercellular channels provide the exchange of small molecules ( 1,000 D), like second messengers, between the cells and they allow electrical coupling. Thus, these cells connected to each other form a syncytium. However, from mapping studies it became evident that under certain conditions, e.g. regional ischemia, the ischemic region uncouples. In addition, mapping studies demonstrated that there is a special activation pattern which accounts for a directed activation of the whole heart. This activation pattern exhibits a considerable similarity from beat to beat. It is well known that the conduction velocity varies between 

3 and 0.6 m/s in the ventricles and 1.0 m/s in the Purkinje system. On the other hand conduction is delayed in the AV node. In addition, the activation has to be transduced from the sinuatrial node to the atria, and from the endings of the Purkinje fibers to the ventricular myocytes. Thus, the coupling within the tissue and between various cells becomes an important feature to provide the normal impulse conduction. From the above-mentioned considerations an association of the different functions and demands with different types of coupling can be concluded. Thus, in general, Cx40 can be found in the conduction system whereas ventricular myocytes are coupled by Cx43. In this chapter, the distribution of the various connexins within the cardiac tissue will be described. First, the distribution of the gap junction channels within a cell will be outlined. 

From figure 9 it becomes clear that the fascia adherens is located transverse to the fiber axis on the cell processes and at the side walls of these processes gap junctions are located in clusters and desmosomes. According to Hoyt et al. [1989] the gap junctions are arranged in a more or less ribbon-like fashion 

The relatively new technique of laser scanning confocal microscopy enabled the determination of the number of gap junctions within one disk to be in the order of 50 or even more [Gourdie et al., 1990] with a diameter of up to 1.3 pm/gap junction. Within the gap junction the channels themselves are arranged as parallel pipe-like structures. From freeze-fractured junctions it has been estimated that about 12.9 103 channels are located in 1 pm2 gap junction (rat right ventricular myocardium) [Chen et al., 1989]. 

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Anisotropy and nonuniformity are at least in part due to inhomogeneities in the distribution of gap junctions and the biophysical properties of the tissue are in fact influenced by the intercellular coupling. At least four features have to be considered. (1) Cardiac cells express different gap junction proteins (so-called connexins in the heart, connexin 40, connexin 43 and connexin 45 are most abundantly found for details see chapters 2 and 3). Channels formed by these connexins are different with regard to their biophysical properties. In various parts of the heart the content of each of these isoforms is different. 

In this chapter changes in the distribution of gap junctions within the myocardial tissue, alterations of the distribution of special isoforms in the course of heart disease are described. Thus, changes in gap junction pattern for Cx43 and for Cx40 in the border zone of a chronic infarction are pointed out. Changes with growing age and in the course of heart failure are discussed as well. 

In patients suffering from heart failure due to ischemic cardiomyopathy Severs [1994a, b] described two main alterations (1) changes in the normal spatial distribution of gap junctions at the border zone of healed infarcts, and (2) a reduction in the quantity of Cx43 in regions distant from infarct scars. 

Fig. 9. Distribution of the gap junctions, desmosomes and fascia adherens in an intercalated disk of a cardiomyocyte as assessed by electron microscopy of freeze-fractured rat and rabbit hearts according to Severs [1990]. 

Conduction disturbances are frequently found in acute and chronic Chagas disease. In cultures of neonatal rat hearts, changes in the gap junction distribution were studied to discover whether they were associated with the infection. In cultured cardiomyocytes infected with the unicellular parasite Trypanosoma cruzi responsible for Chagas disease, which is the most common cause of heart disease in South America, reduced gap junctional conductance... 

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