Abstract 10030: Ultrastructural Analysis of the Cardiomyocyte Perinexus Points totThe Potential for Conduction by Extracellular Electrodiffusion
Cardiomyocyte gap junctions (GJs) composed of connexin43 (Cx43) are aggregates of intercellular channels that contribute to propagation of the action potential in the heart. We recently demonstrated that the region around the GJ [[Unable to Display Character: –]] the perinexus [[Unable to Display Character: –]] is important for regulation of GJ size and communication and reported that interactions between Cx43 and Nav1.5 are concentrated in this region. We hypothesized that the location of molecular constituents correlate to the functional ultrastructure of the perinexus. Transmission electron microscopy was used to image the intercalated disc (ID) in adult rat heart sections. Focusing on GJs in the ID, the intermembrane distance of the perinexal cleft (i.e. the space between the membranes of two cells created by the separation of those membranes at the GJ edge) was measured. On average, the intermembrane distance rose from 0nm to over 10nm within 20nm from the GJ edge, and leveled out to approximately 13nm, which was maintained over a distance of at least 300nm from the GJ edge. However, when taking anomalous features into account, we found that cleft profiles could be subdivided into four groups: the ID edge, rapidly widening clefts, slowly widening clefts, and clefts with vesicles that had opened onto the intermembrane space. These profiles and correlation of their relative frequency to measurement of Cx43 labeling in the perinexus were used to generate a model indicating that the perinexus may be a site of delivery for new connexin43 channels. We infer that regions of close membrane apposition are in the process of active remodeling of the GJ edge. The combination of narrow intermembrane distance and focal concentration of Cx43 and Nav1.5 indicates the potential for cell-to-cell transmission of electrical activation via an electric field mechanism within the perinexus. Further understanding of the structure and function of the perinexus could lead to a paradigm shift in concepts of how propagation of electrical signals occur in the heart.
- © 2012 by American Heart Association, Inc.