The acute toxic effects of silver nanoparticles on myocardial transmembrane potential, INa and IK1 channels and heart rhythm in mice
The acute toxic effects of silver nanoparticles on myocardial transmembrane potential, INa and IK1 channels and heart rhythm in mice
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纳米银对小鼠心肌跨膜电位、INa、IK1通道及心律的急性毒性作用
DOI：
10.1080/17435390.2017.1367047
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发表时间：
2017-01-01
期刊：
影响因子：
5
通讯作者：
Cao, Ji-Min
中科院分区：
文献类型：
--
作者：
Lin, Cai-Xia;Yang, Su-Yu;Cao, Ji-Min
本研究主要关注银纳米颗粒（AgNPs）对心脏电生理的潜在毒性，这一点很少被研究。我们发现AgNPs（10（-9）-10（-6）μ g/ml）浓度依赖性地使小鼠离体心脏乳头肌细胞静息电位去极化，动作电位降低，最终导致兴奋性丧失。在培养的乳鼠心肌细胞上，AgNPs（10（-9）-10（-7）μ g/ml）浓度依赖性地降低Na+电流（I-Na），加速激活，延迟Na+通道失活和在5 min内从失活恢复。AgNPs（10（-8）μ g/ml）也迅速降低内向整流K+电流（I-K1），延迟I-K1通道的激活。静脉注射3 mg/kg的AgNPs仅降低心率，而>= 4 mg/kg则依次诱导窦性心动过缓、完全性房室传导阻滞和心脏停搏。10（-10）-10（-6）g/ml的AgNPs在5 min内不增加活性氧（ROS）的产生，仅在10（-6）g/ml时轻度诱导心肌细胞乳酸脱氢酶（LDH）的释放。2016年05月05日05：00 PM（
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 (I-Na), 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 (I-K1) and delayed the activation of I-K1 channels. Intravenous injection of AgNPs at 3mg/kg only decreased the heart rate, while at >= 4mg/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+ (