Automaticity will be studied in cardiac muscle, especially ventricular myocardium, using depolarization induced pacemaker activity in papillary muscle as the primary model. Major goals will be (1.) Define the characteristics of the pacemaker current previously described under this project, investigate the other outward currents in this tissue, and relate both to its normal electrical behavior. (2.) Investigate a number of possible potassium channel blocking drugs for possible use as tools in membrane studies. (3.) Study the role of endogenous amines in modulating suceptibility of ventricular muscle to depolarization induced automaticity. (4.) Evaluate the effects of antiarrhythmic drugs on outward currents and on automaticity. (5.) Study the relationship of digitalis effects on the ventricular cell membrane to post-cardioversion arrhythmias. Voltage clamp and computer simulation techniques will be used.