TISSUE-SPECIFIC DETERMINANTS OF ANISOTROPIC CONDUCTION-VELOCITY IN CANINE ATRIAL AND VENTRICULAR MYOCARDIUM

Electrical conduction is very rapid and highly anisotropic in atrial fiber bundles, such as the crista terminalis. In contrast to left ventricular myocardium in which the ratio of longitudinal to transverse conduction velocities is approximate to 3, propagation velocity in the crista terminalis is approximate to 10 times greater in the longitudinal than in the transverse direction. To elucidate potential determinants of these distinct conduction properties, we characterized structural and molecular features of intercellular coupling in the crista terminalis and left ventricular myocardium of the canine heart. Analysis of the number and spatial orientation of myocyte interconnections at gap junctions revealed that a typical left ventricular myocyte was connected to 11.3+/-2.2 other myocytes. Approximately equal numbers of connections occurred between ventricular myocytes juxtaposed in side-to-side and end-to-end orientation. In contrast, a typical myocyte of the crista terminalis was connected to only 6.4+/-1.7 other cells (P<.05), but nearly 80% of these connections occurred between cells oriented in an end-to-end configuration. In comparison with the ventricular pattern, this spatial distribution of connections would limit intercellular current transfer between laterally apposed cells and thereby enhance anisotropy of conduction velocity in the longitudinal and transverse directions. Ultrastructural analysis showed that crista terminalis myocytes were connected by numerous small gap junctions that occurred in relatively simple, straight intercalated disks. Northern blot analysis showed approximately equivalent amounts of mRNAs encoding the gap junction channel proteins connexin43 and connexin45 but approximately four times more connexin40 mRNA in crista terminalis than in the left ventricle. Immunocytochemical studies with connexin-specific antibodies revealed far more intense connexin40 signal in crista terminalis than in left ventricular muscle. Thus, myocytes of the crista terminalis and left ventricular subepicardium differ markedly in the number and spatial distribution of their intercellular junctions and in the molecular composition of their gap junction proteins. These structural and molecular features likely contribute to the distinct anisotropic conduction properties characteristic of the two tissues. ,