Multidisciplinary research will be aimed at the molecular and electrophysiologic bases of propagation in cardiac muscle. We will study the mechanisms of gap junction channel regulation, as well as the role of intercellular communication in cardiac impulse propagation, and well determine the quantitative bases or regular and irregular dynamics of excitation and impulse propagation. There is a need to address these fundamental problems. By using a multi-level approach detailed identification of the mechanisms of electrical communication may be accomplished. Our experimental strategies will include: 1)Use of single cell current and voltage clamp techniques to investigate the ionic basis of heart rate-dependant excitability and conduction abnormalities. 2) Measurement of membrane electrical properties in cardiac muscle tissues and in single cells, both under control conditions and in response to drugs. 3) Use of computer-aided high resolution optical mapping techniques to investigate the roles of electrical coupling, active generator properties and fiber orientation on cardiac impulse propagation. 4) Use of chaos theory and electrophysiologic techniques to elucidate the mechanisms of heart rate-dependent excitation and conduction disturbances. 5) Use of mathematical simulations and massively parallel supercomputer technology to study normal mechanisms of cardiac impulse propagation. 6)Use of a double patch clamp technique to investigate gap junctional conductance regulation in pairs of heart cells. 7)Use of biochemical, recombinant DNA, ultrastructural and electrophysiologic techniques to isolate, and characterize gap junction proteins of cardiac muscle in heterologous systems. 8) Preparation of antibodies against gap junction proteins. 9)Use of pharmacologic and immunochemical probes to study control of impulse propagation in isolated cardiac tissues and in paris of dissociated heart cells. Description of all these important factors is essential for improving diagnosis, treatment and prevention of cardiac rhythm disturbances.
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