Multiple effects of calcium antagonists on plateau currents in cardiac Purkinje fibers

We studied the influence of Mn, La, and D600 on action potentials and plateau currents in cardiac Purkinje fibers. The Ca antagonists each abolished the second inward current, but they failed to act selectively. Voltage clamp experiments revealed two additional effects: decrease of slow outward current (iotachi) activation, and increase of net outward time-independent plateau current. These effects occurred at inhibitor concentrations used in earlier studies, and were essential to the reconstruction of observed Ca antagonist effects on electrical activity. The inhibitory influence of Mn, La, and D600 on iotachi suggested that iotachi activation might depend upon prior Ca entry. This hypothesis was not supported, however, when [Ca]omicron was varied: elevating [Ca]omicron enhanced Ca entry, but iotachi was nevertheless depressed. Thus, the results suggested instead that Ca antagonists and Ca ions have rather similar effects on iotachi, possibly mediated by changes in membrane surface charge.