This study focused on the potential toxicity of silver nanoparticles (AgNPs) on cardiac electrophysiology which is rarely investigated. We found that AgNPs (10-10g/ml) concentration-dependently depolarized the resting potential， diminished the action potential， and finally led to loss of excitability in mice cardiac papillary muscle cells in vitro. In cultured neonatal mice cardiomyocytes， AgNPs (10-10g/ml) concentration-dependently decreased the Na currents (I)， accelerated the activation， and delayed the inactivation and recovery of Na channels from inactivation within 5 min. AgNPs at 10g/ml also rapidly decreased the inwardly rectifying K currents (I) and delayed the activation of I channels. Int... More
This study focused on the potential toxicity of silver nanoparticles (AgNPs) on cardiac electrophysiology which is rarely investigated. We found that AgNPs (10-10g/ml) concentration-dependently depolarized the resting potential， diminished the action potential， and finally led to loss of excitability in mice cardiac papillary muscle cells in vitro. In cultured neonatal mice cardiomyocytes， AgNPs (10-10g/ml) concentration-dependently decreased the Na currents (I)， accelerated the activation， and delayed the inactivation and recovery of Na channels from inactivation within 5 min. AgNPs at 10g/ml also rapidly decreased the inwardly rectifying K currents (I) and delayed the activation of I channels. Intravenous injection of AgNPs at 3 mg/kg only decreased the heart rate， while at ≥4 mg/kg sequentially induced sinus bradycardia， complete atrio-ventricular conduction block， and cardiac asystole. AgNPs at 10-10g/ml did not increase reactive oxygen species (ROS) generation and only at 10g/ml mildly induced lactate dehydrogenase (LDH) release in the cardiomyocytes within 5 min. Endocytosis of AgNPs by cardiomyocytes was not observed within 5 min， but was observed 1 h after exposing to AgNPs. Comparative Ag (≤0.02% of the AgNPs) could not induce above toxicities. We conclude that AgNPs exert rapid toxic effects on myocardial electrophysiology and induce lethal bradyarrhythmias. These acute toxicities are likely due to direct effects of AgNPs on ion channels at the nano-scale level， but not caused by Ag， ROS， and membrane injury. These findings provide warning to the nanomedical practice using AgNPs.
