Acute alteration of cardiac ECG, action potential, I(Kr) and the human ether-a-go-go-related gene (hERG) K+ channel by PCB 126 and PCB 77.
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.
Department of Physiology, Institute of Bioscience and Biotechnology, Kangwon National University College of Medicine, Chuncheon 200-701, Republic of Korea.
Mi-Hyeong
MH
Park
Won Sun
WS
Park
Su-Hyun
SH
Jo
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D051668:Delayed Rectifier Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography; D004785:Environmental Pollutants / Q000633:toxicity; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009865:Oocytes; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D014982:Xenopus laevis
D051668:Delayed Rectifier Potassium Channels; D000072237:ERG1 Potassium Channel; D004785:Environmental Pollutants; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D011078:Polychlorinated Biphenyls; D002118:Calcium; C023035:3,4,5,3',4'-pentachlorobiphenyl; C028451:3,4,3',4'-tetrachlorobiphenyl