Depolarization-induced Movement of Mn 2 Cations Across the Cell Membrane in the Guinea Pig Myocardium

The effects of Mn-2+-containing solutions on the mechanical and electrical responses of myocardial tissue were studied on guinea pig ventricular strips. At a concentration of 10 mM, Mn-2+ abolished the twitch responses and caused the development of a contracture in stimulated preparations but not in resting or in Ca-2+-depleted preparations. The duration of action potentials was shortened, and dV/dt-max was decreased. In Ca-2+-depleted (0.1 mM), Mg-2+-free medium, Mn-2+ also increased the amplitude of the overshoot; the increase was due to a slow phase of depolarization. Measurement of the Mn-2+ uptake showed an increased influx of these ions in stimulated preparations compared with that in quiescent preparations. These results suggest that Mn-2+ (1) generates a transmembrane current in guinea pig myocardial cells and (2) interferes with the excitation-contraction coupling process at two levels: the cell membrane and an intracellular site.