The acute toxic effects of silver nanoparticles on myocardial transmembrane potential, INa and IK1 channels and heart rhythm in mice.

摘要

This study focused on the potential toxicity of silver nanoparticles (AgNPs) on cardiac electrophysiology which is rarely investigated. We found that AgNPs (10(-9)-10(-6 )g/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(-9)-10(-7 )g/ml) concentration-dependently decreased the Na(+) currents (INa), accelerated the activation, and delayed the inactivation and recovery of Na(+) channels from inactivation within 5 min. AgNPs at 10(-8 )g/ml also rapidly decreased the inwardly rectifying K(+) currents (IK1) and delayed the activation of IK1 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(-10)-10(-6 )g/ml did not increase reactive oxygen species (ROS) generation and only at 10(-6 )g/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(+) (

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