Distinct gap junction protein phenotypes in cardiac tissues with disparate conduction properties

Department of Pediatrics, Washington University School of Medicine, Saint Louis, Missouri 63110.

OBJECTIVES. We sought to characterize the connexin phenotypes of selected regions of the canine heart with different conduction properties to determine whether variations in connexin expression might contribute to the differences in intercellular resistance and conduction velocity that occur in different cardiac tissues. BACKGROUND. Gap junctions connect cardiac myocytes, allowing propagation of action potentials. Intercellular channels with different electrophysiologic properties are formed by different connexin proteins. METHODS. To determine which connexins were likely to be expressed in the sinus node, atrioventricular (AV) node and atrial and ventricular myocardium, messenger ribonucleic acids (RNAs) from each of these sites were hybridized with probes for connexin26, connexin31, connexin32, connexin37, connexin40, connexin43, connexin45, connexin46 and connexin50. Immunostaining with monospecific antibodies to connexin40, connexin43 and connexin45 was used to delineate the distribution of connexins in frozen sections of these different cardiac tissues. RESULTS. Only messenger RNAs coding for connexin40, connexin43 and connexin45 were detected by Northern blot analysis. By immunohistochemical staining, junctions in the sinus and AV nodes and proximal His bundle were virtually devoid of connexin43 but contained both connexin40 and connexin45. Gap junctions in the distal His bundle and the proximal bundle branches stained intensely for connexin40 and connexin43 and to a lesser extent for connexin45. Atrial gap junctions showed abundant staining of connexin43, connexin40 and connexin45. Ventricular gap junctions were characterized by abundant staining of connexin43 and connexin45 and much less staining of connexin40. CONCLUSIONS. Although most cardiac gap junctions contain connexin40, connexin43 and connexin45, the relative amounts of each of these connexins vary considerably in cardiac tissues with different conduction properties.

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