INTERCELLULAR COUPLING AND PROPAGATION IN CARDIAC TISSUE

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Previous investigations from our laboratory have shown that heart rate- dependent and intermittent block processes, such as during Wenckebach periodicity in atrioventricular (AV) transmission, cannot be explained merely on the basis of slow conduction, and are not compatible with behavior expected form a homogeneous system of electrically coupled cells. In addition, it has been suggested that alterations in cell-to-cell coupling and other passive membrane properties may play a significant role in the development of conduction block processes in all types of cardiac tissue. It is our purpose to characterize the excitability properties of the AV nodal cells, and the propagation characteristics of the isolated rabbit AV node, as they pertain to the development of rate-dependent AV conduction disturbances and arrhythmias. Moreover, we will study uniform and non-uniform anisotropy in ventricular epicardial muscle, and will correlate propagation patterns with the geometrical distribution of intercellular communication. A combination of single-electrode current and voltage clamp techniques in single AV node cells, as well as high resolution optical mapping, electrophysiological recordings and immunohistochemical techniques, will be used toward the following specific aims: 1) To investigate the ionic mechanisms of rate-dependent excitation patterns in the single AV nodal cell. 2) To identify the precise activation sequence of the isolated rabbit atrioventricular node and its correlation with cell type and gap junction distribution, and 3) To characterize anisotropic propagation in ventricular epicardial muscle as it relates to the applicability of the continuous medium theory. These studies should improve our understanding of the factors involved in the ability of the cardiac tissues to conduct electrical impulses. The results should give also precise and direct answers about the ionic bases of conduction block processes with alternation or with Wenckebach periodicity.