Effects of amrinone and milrinone on calcium influx into the myocardium.

We have examined the effects of milrinone on calcium influx into cardiac cells by testing its effects on three mechanisms of calcium entry: the slow inward calcium current, sodium-calcium exchange diffusion, and the passive calcium permeability of sarcolemmal membranes. Milrinone increased the magnitude of the slow inward calcium current in voltage-clamped calf cardiac Purkinje fiber. High concentrations of this agent also caused a small, inconsistent inhibition of calcium uptake mediated by sodium-calcium exchange in bovine cardiac sarcolemma membranes, but did not alter the time course of passive efflux of calcium from these vesicles. In conclusion, milrinone and its analogue amrinone appear to increase the entry of calcium into myocardial cells, primarily by increasing the influx of this cation during the slow inward calcium current. A small and sodium-calcium exchange may also influence calcium influx, particularly at high drug concentrations. The relationship existing between these effects and the inotropic responses produced by amrinone and milrinone is discussed.