Cardiac Myosin and Thin Filament as Targets for Lead and Cadmium Divalent Cations

Lead and cadmium are heavy metals widely distributed in the environment and contribute significantly to cardiovascular morbidity and mortality. Using Leadmium Green dye, we have shown that lead and cadmium enter cardiomyocytes, distributing throughout the cell. Using an in vitro motility assay, we have shown that sliding velocity of actin and native thin filaments over myosin decreases with increasing concentrations of Pb2+ and Cd2+. Significantly lower concentrations of Pb2+ and Cd2+ (0.6 mM) were required to stop sliding of thin filaments over myosin compared to the stopping actin sliding over the same myosin (1.1-1.6 mM). Lower concentration of Cd2+ (1.1 mM) needed to stop actin sliding over myosin compared to the Pb2++Cd2+ combination (1.3 mM) and lead alone (1.6 mM). There were no differences found in the effects of lead and cadmium cations on relative force developed by myosin heads or number of actin filaments bound to myosin. Sliding velocity of actin over myosin in the left atrium, right and left ventricles changed equally when exposed to the same dose of the same metal. Thus, we have demonstrated for the first time that Pb2+ and Cd2+ can directly affect myosin and thin filament function, with Cd2+ exerting a more toxic influence on myosin function compared to Pb2+.