Related Experiment Video
Updated: Jun 14, 2025
Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling
Published on: August 1, 2016
Cardiac Myosin and Thin Filament as Targets for Lead and Cadmium Divalent Cations
Oksana P Gerzen1, Iulia K Potoskueva2, Alena E Tzybina2
1Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences, Ekaterinburg, 620078, Russia. o.p.gerzen@gmail.com.
Insights
Heavy metals like lead and cadmium impair heart muscle cell function by directly impacting myosin and thin filament function. Cadmium (Cd2+) shows a more toxic effect on myosin than lead (Pb2+).
Area of Science:
- Cardiovascular toxicology
- Cellular mechanics
- Environmental health
Background:
- Lead (Pb2+) and cadmium (Cd2+) are pervasive environmental heavy metals linked to cardiovascular disease.
- Cardiomyocytes are susceptible to heavy metal toxicity, impacting cardiac function.
Purpose of the Study:
- To investigate the direct effects of lead and cadmium on cardiomyocyte function at the molecular level.
- To determine the specific mechanisms by which these heavy metals impair cardiac contractility.
Main Methods:
- Utilized Leadmium Green dye to track heavy metal entry and distribution within cardiomyocytes.
- Employed an in vitro motility assay to measure the impact of Pb2+ and Cd2+ on actin-myosin interactions.
- Assessed changes in sliding velocity, force generation, and filament binding.
Main Results:
- Both lead and cadmium enter cardiomyocytes and distribute throughout the cell.
- Increasing concentrations of Pb2+ and Cd2+ significantly decrease actin-myosin sliding velocity.
- Cadmium (Cd2+) inhibited thin filament sliding at lower concentrations (0.6 mM) than lead (Pb2+) (1.1-1.6 mM).
- Cd2+ also inhibited actin sliding over myosin at a lower concentration (1.1 mM) compared to Pb2+ alone (1.6 mM).
- No significant differences were observed in the effects on myosin head force generation or actin filament binding.
Conclusions:
- Demonstrated for the first time that Pb2+ and Cd2+ directly impair myosin and thin filament function in cardiomyocytes.
- Cd2+ exhibits a more potent toxic effect on myosin function compared to Pb2+.
- These findings provide molecular insights into the cardiovascular toxicity of lead and cadmium.
Abstract:
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+.
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