Reversal of caffeine-induced calcium overload in cardiac Purkinje fibers.

In cardiac Purkinje fibers, caffeine initially increases and then decreases contractile force. The possible role of calcium overload in the negative inotropic effect of caffeine was studied in vitro under conditions that have been demonstrated to increase or decrease cellular calcium. The following results were obtained. Increasing [K]0 increased the initial positive and decreased the subsequent negative inotropic effect of 1 mM caffeine. At higher concentrations (2 and 4 mM), caffeine induced a larger negative inotropic effect which was reversed by high [K]0. Similarly, the positive inotropic effect was increased and the negative decreased by lowering [Ca]0. In high [Ca]0 or low [Na]0, caffeine had a predominantly negative inotropic effect which also was reversed by adding tetrodotoxin or by high [K]0. Reciprocally, in high [K]0, increasing [Ca]0 restored the negative inotropic effect of caffeine. During a brief exposure to zero [Ca]0, the force fell in the absence but less or not at all in the presence of caffeine. It is concluded that caffeine decreases contractile force in cardiac Purkinje fibers mostly by causing calcium overload.