Serious ventricular arrhythmias often occur in man immediately after a coronary occlusion, as well as for weeks to years after the infarction. Ventricular ectopy also occurs after the onset of experimentally produced myocardial infarction in the dog heart. Transmembrane action potentials from subendocardial Purkinje fibers that survive infarction (24hr) resulting from coronary artery occlusion in the dog have reduced resting potentials, slow rates of depolarizations, enhanced diastolic depolarization and prolonged durations. It has been suggested that one or more of these electrophysiologic abnormalities and structural changes that occur may lead to ventricular arrhythmias. Therefore, the mechanisms for these electrophysiologic changes may be important to understand in terms of developing therapeutic interventions. It is our aim to identify and quantify the ionic mechanisms of these abnormalities using disaggregated single cells, standard microelectrode and voltage clamp techniques. Specifically, we will disaggregate single Purkinje cells from the subendocardium of the noninfarcted heart, and Purkinje cells from the subendocardium of the infarcted heart (24hr). Electrophysiological and ultrastructural studies will be done on these cells the results of which will be compared to the results of our studies on Purkinje cells disaggregated from free running fiber bundles. We will determine the basis for a difference in resting potential between groups by determining PNa/Pk ratios, by measuring intracellular K+ and Na+ concentrations, and by determining steady state Na-K pump contribution to membrane potential. In addition, we will characterize Na-K pump function in both cell groups and compare the results. Interventions will be used to both inhibit and stimulate the Na-K pump and the effects on membrane potential and net membrane currents determined. We will combine voltage clamp techniques and microelectrode techniques to determine what alterations in ionic permeabilities underlie the differences in rates of depolarization, action potential amplitude and action potential duration of the cells in the different groups. Furthermore, we will determine the ionic mechanism underlying phase 4 depolarization if it is found in the isolated control cell, and compare it to phase 4 depolarization that is seen in Purkinje cell from the endocardium of the infarcted myocardium.