Very little is known about the interactions of nerve terminals in the developing heart. This application proposes a continuing study of these interactions by removal of the autonomic and sensory neural precursors in various combinations. The lesions will be accomplished in early chick embryos by selective cauterization of the neural crest producing presumptive parasympathetic, or sympathetic postganglionic neurons or the nodose placodes from which the sensory cardiac innervation arises. Two major questions have been asked: what interactions occur among terminals of the remaining innervation, and what interactions occur between these terminals and the developing myocardium.
The aims of this application are to compare the configuration of normal innervation with that in the absence of any of the three sets of cardiac nerves and then to evaluate the effect of this abnormal neural environment on development of myocardial electrical activity, myocardial intermediary metabolism and myocardial myosin development. The remaining innervation will be evaluated both quantitatively using a variety of histological and histochemical methods. Electrical activity of the myocardium will be evaluated by electrocardiography; myocardial energy metabolism will be studied using quantitative histochemical methods; and myosin development will be assessed quantitatively and qualitatively by determining myosin ATPase activity and by analysis of intact myosin by native gel electrophoresis. It is hoped that this continuing study of the dynamic relationship between the heart and the nerves which control it will lead to effective recognition and treatment of cardiac dysfunctions such as long QT syndrome and hypertrophic cardiomyopathy.
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