This proposal requests support to purchase equipment (a central computational unit) that will be used to fulfill the computer modeling, data processing and data analysis needs of 7 independent investigators working the Departments of Pharmacology, Microbiology and Medicine at the SUNY Health Science Center in Syracuse, NY. The program represents a multidisciplinary approach whose overall objective is to achieve an understanding of normal and abnormal electrical wave propagation in cardiac muscle. Our efforts are directed toward elucidating the underlying two- and three-dimensional dynamics of wave propagation in the heart and the mechanisms of reentrant ventricular tachyarrhythmias, as well as the structure-function relations that determine gating behavior of the major cardiac gap junction (Cx43) protein and of a delayed rectifier potassium channel (HERG) which as been cloned from human tissue. The central theme, """"""""Intercellular Communication and Impulse Propagation"""""""", addresses an important scientific topic of clinical relevance, and allows the unique opportunity of bringing together a group of investigators, experts in various relevant fields, including cellular electrophysiology, biophysics, biomedical engineering, mathematics, computer science and molecular biology, in a productive cooperative research program. Major support of this program comes from a Program Project Grant (PO1 HL39707) from the National Heart Lung and Blood Institute. Support is provided also by the American Heart Association and the North American Society of Pacing and Electrophysiology. In addition, funding is pending from the Whitaker Foundation, as well as from NIH in the form of RO1 grant of two of our investigators. Continuous finding of our research group since 1982 has been exceedingly fruitful. For example, over the last 5 years we have published 85 peer-review papers and have contributed significantly to the understanding of fundamental mechanisms of intercellular communication and impulse propagation. A major strength of our group is its ability to successfully complement experimental studies on the cellular mechanisms of propagation of electrical impulses under normal and abnormal conditions with computer modeling studies aimed at predicting heart tissue behaviors. Computer models are an essential tool to formulate hypotheses regarding ionic mechanisms, and propagation dynamics of the genesis of cardiac arrhythmias. It is our goal to continue using such a combined experimental-computer modeling approach in our future studies.
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