Caffeine-induced Ca2+ release activates Ca2+ extrusion via Na+-Ca2+ exchanger in cardiac myocytes.

Rapid application of caffeine in fura-2-dialyzed and whole cell-clamped rat and guinea pig ventricular myocytes activated reversibly large intracellular Ca2+ transients that accompanied Na+-dependent transient inward currents. Such transient inward currents had the same time course as the intracellular Ca2+ transient and were suppressed by Ni2+ and removal of extracellular Na+. Because Ca2+ release signals were not altered by addition of Ni2+ or removal of Na+, we concluded that the rise in intracellular Ca2+ concentration was necessary for the activation of the transient inward current. Thus the caffeine-induced transient inward current represents efflux of Ca2+ via the Na+-Ca2+ exchanger.