Digitalis affects cardiac function by inhibiting:
Therapeutic use of foxglove extracts containing digoxin and digitoxin dates to Withering eighteenth century for dropsy. Molecular target identified as sodium potassium ATPase, P-type pump maintaining high potassium low sodium intracellular, essential for cardiac electrophysiology. Digitalis glycosides bind extracellular vestibule formed by transmembrane segments of alpha subunit in E2P conformation, competing with potassium and locking enzyme in phosphorylated outward open state, inhibiting cycle. Inhibition fraction modest at therapeutic concentrations about 20 to 40 percent raises submembran
Ref: Withering and Hauptman, Digitalis and Na+/K+ ATPase Inhibition Cardiac Glycoside Mechanism.
