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.

Mi-Hyeong Park, Won Sun Park, Su-Hyun Jo

Index: Toxicol. Appl. Pharmacol. 262(1) , 60-9, (2012)

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Abstract

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.Copyright © 2012 Elsevier Inc. All rights reserved.