Relationship between caffeine effects and calcium in canine cardiac Purkinje fibers

The actions of caffeine (1-9 mM) on electrical and mechanical events were studied under conditions known to change the intracellular calcium in canine cardiac Purkinje fibers perfused in vitro. It was found that caffeine in a dose-dependent manner 1) shifts the early repolarization to more positive values, 2) shifts the plateau to more negative values, 3) prolongs the terminal phase 3 (induction of a "tail"), 4) transiently increases and then decreases the force of contraction with respect to control values, 5) causes a smaller tail in the presence of agents (local anesthetics, tetrodotoxin, high potassium) that have been shown to diminish the force of contraction, presumably by decreasing cellular calcium, 6) causes the oscillatory potentials in high calcium to peak sooner after the action potential and eventually to disappear as the tail develops, 7) induces a tail at lower concentrations when cellular calcium is enhanced by lowering the external sodium concentration or in the presence of veratridine, and 8) fails to induce a marked tail in the presence of metabolic inhibitors. It is concluded that in Purkinje fibers caffeine induces a marked delay in the final repolarization through a process modulated by calcium. This process may be related to an electrogenic sodium-calcium exchange.