The effects of equipotent concentrations of diltiazem, verapamil, and nifedipine upon the accumulation of extracellular potassium IK + lout and the left ventricular pressure (LVP) were studied during global ischemia in isolated perfused rat hearts. Measurement of [K+]out and LVP were performed in two series of experiments. Diltiazem (2 x 10 -6, 3 Γ 10 -e, and 10 -5 M), verapamil (3 x 10 -s, 10 -7, and 3 x 10 -7 M), and nifedipine (3 x 10 -s, 10 -7, and 1.5 x 10 -7 M) were able to slow, in a concentration-dependent manner, the initial rate of rise of [K+]out without affecting the final plateau value of [K+]out reached at t = 5 to t --10 minutes. Notably, at the lowest concentrations, which slightly influenced LVP diltiazem, verapamil, and to a lesser degree nifedipine, were still able to slow the rise in [K+]out. In addition, after preperfusion with low-calcium media ([Ca 2+ ] from 1.8 to 1.3 or 0.9 mM), inducing similar negative inotropic effects as those of the calcium antagonists, the rise in [K+]out was not significantly influenced. Our data indicate that the ability to slow the rise in [K+ lout is a specific characteristic of calcium antagonists that is independent of their negative inotropic effects.