Cellular electrophysiology of digitalis toxicity

The toxic effects of digitalis are attributable in part to poisoning of the enzyme Na+-K+ ATPase and in part to the interactions of digitalis with the sympathetic and parasympathetic nervous systems. Additional modifiers of the toxic effects of digitalis include the concentrations of ions such as K+ and Ca2+, the age of the subject and the extent and type of cardiac disease. At the cellular electrophysiologic level, digitalis toxicity is seen as a depolarization of the membrane with the occurrence--individually or simultaneously--of abnormalities of impulse initiation (including delayed afterdepolarizations and abnormal automaticity) and abnormalities of conduction. The afterdepolarizations result in triggered arrhythmias that differ partially in their characteristics of onset and termination from automatic and reentrant arrhythmias. The cellular electrophysiologic basis for these arrhythmias induced by toxic concentrations of digitalis and their implications with respect to arrhythmogenesis in the in situ heart are explored in detail.