Department of Physiology, Institute of Bioscience and Biotechnology, Kangwon National University College of Medicine, Chuncheon 200-701, Republic of Korea.
Toxicol Appl Pharmacol. 2012 Jul 1;262(1):60-9. doi: 10.1016/j.taap.2012.04.019. Epub 2012 Apr 28.
Polychlorinated biphenyls (PCBs) have been known as serious persistent organic pollutants (POPs), causing developmental delays and motor dysfunction. We have investigated the effects of two PCB congeners, 3,3',4,4'-tetrachlorobiphenyl (PCB 77) and 3,3',4,4',5-pentachlorobiphenyl (PCB 126) on ECG, action potential, and the rapidly activating delayed rectifier K+ current (I(Kr)) of guinea pigs' hearts, and hERG K+ current expressed in Xenopus oocytes. PCB 126 shortened the corrected QT interval (QTc) of ECG and decreased the action potential duration at 90% (APD(90)), and 50% of repolarization (APD₅₀) (P<0.05) without changing the action potential duration at 20% (APD₂₀). PCB 77 decreased APD₂₀ (P<0.05) without affecting QTc, APD₉₀, and APD₅₀. The PCB 126 increased the I(Kr) in guinea-pig ventricular myocytes held at 36°C and hERG K+ current amplitude at the end of the voltage steps in voltage-dependent mode (P<0.05); however, PCB 77 did not change the hERG K+ current amplitude. The PCB 77 increased the diastolic Ca²⁺ and decreased Ca²⁺ transient amplitude (P<0.05), however PCB 126 did not change. The results suggest that PCB 126 shortened the QTc and decreased the APD₉₀ possibly by increasing I(Kr), while PCB 77 decreased the APD₂₀ possibly by other modulation related with intracellular Ca²⁺. The present data indicate that the environmental toxicants, PCBs, can acutely affect cardiac electrophysiology including ECG, action potential, intracellular Ca²⁺, and channel activity, resulting in toxic effects on the cardiac function in view of the possible accumulation of the PCBs in human body.
多氯联苯 (PCBs) 是一种严重的持久性有机污染物 (POPs)，会导致发育迟缓及运动功能障碍。本研究旨在探讨两种 PCB 同系物，3,3',4,4'-四氯联苯 (PCB 77) 和 3,3',4,4',5-五氯联苯 (PCB 126) 对豚鼠心脏心电图 (ECG)、动作电位和快速激活延迟整流钾电流 (I(Kr))，以及 Xenopus 卵母细胞中表达的 hERG 钾电流的影响。结果发现，PCB 126 缩短了 ECG 的校正 QT 间期 (QTc)，并降低了 90%复极化时程 (APD(90)) 和 50%复极化时程 (APD₅₀) (P<0.05)，但对 20%复极化时程 (APD₂₀) 没有影响。PCB 77 降低了 APD₂₀ (P<0.05)，但不影响 QTc、APD₉₀ 和 APD₅₀。PCB 126 增加了 36°C 下豚鼠心室肌细胞的 I(Kr)和电压依赖性模式下电压步末 hERG 钾电流幅度 (P<0.05)；然而，PCB 77 并未改变 hERG 钾电流幅度。PCB 77 增加了舒张期 Ca²⁺并降低了 Ca²⁺瞬变幅度 (P<0.05)，但 PCB 126 没有改变。结果表明，PCB 126 通过增加 I(Kr)缩短 QTc 和降低 APD₉₀，而 PCB 77 通过其他与细胞内 Ca²⁺相关的调制作用降低 APD₂₀。本研究数据表明，环境毒物 PCBs 可急性影响包括心电图、动作电位、细胞内 Ca²⁺和通道活性在内的心脏电生理学，鉴于 PCBs 在人体内可能发生积累，这可能对心脏功能产生毒性作用。
