Using immunohistological and electrophysiological techniques, the applicant has identified a critical stage in embryonic development when the form and function of the His-Purkinje system (HPS) appears as a transition from action potential propagation through the atrioventricular junction (AVJ) to HPS conduction. The applicant hypothesizes that the mechanism underlying the transition from AVJ to HPS conduction can be associated by maturation of the HPS and the breakdown of myocardial connections at the AVJ. To test this hypothesis, the applicant has developed a microscope-based optical mapping system to obtain detailed activation maps of the embryonic chick ventricle at high spatial and temporal resolution. Microscopic optical mapping of the ventricle also provides a sensitive assay to identify the roles of certain molecules in HPS maturation. One molecule present at both the AVJ and on HPS precursors during this transition period is polysialic acid (PSA), a carbohydrate post-translationally added to the cell adhesion molecule NCAM that attenuates cell adhesion and gap junction formation mediated by NCAM and by other adhesion molecules. PSA will be removed enzymatically from heart in vivo, and cellular coupling in the embryonic heart will be electrophysiologically and histologically assessed. An understanding of the processes that govern the emergence of HPS conduction and the termination of AVJ conduction will provide greater insight into the origins of key structures in the AVJ which form the substrate for superventricular tachycardias.
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