The objective is to develop knowledge and basic skills in cellular biology, with a particular emphasis on the function of the myocardial cell. The applicant will initially concentrate on the function of the slow calcium channel under normal conditions. The effects of membrane depolarization upon calcium channel properties will be assessed using radioligand binding techniques, calcium flux studies, single-cell contractility studies and electrophysiology in the cultured heart cells monolayer system. These initial studies will enhance the candidate's understanding of the myocardial cell under normal conditions as well as further understanding of the behavior of the calcium channel. The proposed training program will include coursework at Harvard Medical School as well as the Massachusetts Institute of Technology. Collaborations with other investigators at Brigham and Women's Hospital and Harvard Medical School will broaden the candidate's scientific base. Further studies initiated in phase I will center on complex responses of the myocardial cell to hypoxia and simulated ischemia. Using a specially designed anaerobic chamber and carefully monitored oxygen tensions, radioligand binding and calcium flux studies will be performed in conditions of graded hypoxia. Using an optical video system, single cell contractile function will be studied during the imposition of elements of simulated ischemia including hypoxia and acidosis. The applicant has begun these studies by spending seven months of his senior medical residency in the laboratory of the sponsor. Studies of the myocardial cell under normal conditions and conditions of simulated ischemia will be extended. Additional goals include the development of stable differentiated myocyte lines that would facilitate the study of virtually all aspects of cardiac cell function.
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