It is well known that the contact of catheters with the heart can induce extra beats, and that thumps to athe chest can change the cardiac rhythm. There is growing evidence that mechanical factors associated with abnormal wall motion in athe heart may contribute to arrhythmogenesis via mechanoelectrical coupling. Ventricular arrhythmias are associated with volume or pressure overload resulting from aortic valve disease or dilated cardiomyopathy, and it has been suggested that these may arise in part from myocardial stretch. Studies in more than eleven vertebrate species, including man, confirm the reality of mechanoelectrical coupling. The goal of this basic science research is to test the hypothesis that changes in cell length alter the cell electrophysiology. Isolated preparations offer the advantage of circumventing the confounding influences of the nervous system owing to baroreceptor reflexes and other stretch mediated nervous activity. Studies with these preparations have shown a reduction in resting potential and action potential duration, and induction of after depolarizations and extrasystoles. Measurements of mechanoelectrical coupling in single cells offer the additional possibility for determining the ion channels involved, using voltage clamp techniques. The most likely candidates by which stretch ma affect ion transport across the cell membrane are channels which are mechanosensitive (e.g., stretch- activated). However, such information has been obtained primarily from single channel recordings, with little known about the functional effects of stretch on whole cell currents. The key to this proposal is the ability in our laboratory to manipulate the mechanical load placed on single frog cardiac cells during whole cell voltage clamp. A three year time frame is planned for this project. The specific aims are to test the following hypotheses; 1) Cell excitability and refractoriness are sensitive to stretch, 2) The stretch response is a time-dependent, viscoelastic phenomenon, 3) Changes in cell length gate the so-called "stretch- activated" channel, and 4) Other ionic channels may be stretch-sensitive.