Calcium overload and strophanthidin-induced mechanical toxicity in cardiac Purkinje fibers

In cardiac Purkinje fibers, strophanthidin increases and then decreases contractile force. The relationship between the decrease in force and calcium overload was studied by recording the electrical and mechanical activity under conditions known to increase calcium overload or its effects. Inhibitors of oxidative phosphorylation reduced the positive inotropy of strophanthidin and enhanced the decrease in force. These inhibitors also reduced the inotropic effect of high calcium. Increasing intracellular calcium by decreasing extracellular sodium concentration also resulted in a decrease in the strophanthidin inotropy. When arrhythmia was delayed, strophanthidin induced contracture and this was favored by blockers of glycolysis and by enhancing cellular calcium. Some of these effects were also observed in ventricular muscle fibers but at higher strophanthidin concentrations. The results suggest that the decline in contractile force during strophanthidin exposure is related to calcium overload, although it i...