Digitalis causes several types of cardiac arrhythmias. These arrhythmias could result from different mechanisms such as an enhanced diastolic depolarization, an increased calcium influx, an increased intracellular calcium concentration, an increased sodium influx or the poisoning of the sodium potassium pump. These mechanisms lead to the development of transient oscillations and of small action potentials in the plateau region. The objective of the proposed research project is to investigate the mechanisms of different manifestations of digitalis toxicity. The microelectrode technique will be used to record membrane potential and control voltage, radioisotopes to measure changes in ion movements, and force transducer to measure force of contraction. The mechanism of induction of spontaneous activity in quiescent fibers will be investigated by trying to identify the conductance change which is responsible for the initiation of activity. This will be done by altering ionic environment and measuring ionic currents. The nature of transient oscillations will be explored to find out whether this enhanced calcium effect is a primary or secondary effect of digitalis. The contribution of sodium inward movement and that of sodium outward movement will be related to the electrical and mechanical events which occur at various stages of digitalis toxicity. The altered relationship between sodium and calcium induced by digitalis will be studied by suitably altering the composition of the extra- and intra-cellular compartments. The role of the poisoning of the sodium-potassium pump will be investigated as far as the mechanical and electrical effects are concerned. The mechanism by which different rates of drive precipitate arrhythmias will be analyzed in the presence of strophanthidin. Anti-arrhythmic agents will be studied as to this mechanism of action in suppressing digitalis arrhythmias. Different cardiac tissues will be used for not necessarily each of them respond to digitalis in the same manner.