Non-dioxin-like polychlorinated biphenyl 19 has distinct effects on human Kv1.3 and Kv1.5 channels

• Published in: Toxicology and applied pharmacology 2021-01, Vol.411, p.115365, Article 115365
• Main Authors: Kim, Jong-Hui, Hwang, Soobeen, Jo, Su-Hyun
• Format: Article
• Language: English
• Subjects: Animals; Dose-Response Relationship, Drug; Environmental Pollutants - toxicity; Female; Humans; Kv1.3 channel; Kv1.3 Potassium Channel - antagonists & inhibitors; Kv1.3 Potassium Channel - genetics; Kv1.3 Potassium Channel - metabolism; Kv1.5 channel; Kv1.5 Potassium Channel - drug effects; Kv1.5 Potassium Channel - genetics; Kv1.5 Potassium Channel - metabolism; Membrane Potentials; Oocytes; PCB19; Polychlorinated biphenyls; Polychlorinated Biphenyls - toxicity; Potassium Channel Blockers - toxicity; Time Factors; Xenopus laevis
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2020.115365

Polychlorinated biphenyls (PCBs) are persistent and serious organic pollutants and can theoretically form 209 congeners. PCBs can be divided into two categories: dioxin-like (DL) and non-DL (NDL). NDL-PCBs, which lack aryl hydrocarbon receptor affinity, have been shown to perturb the functions of Jurkat T cells, cerebellar granule cells, and uterine cells. Kv1.3 and Kv1.5 channels are important in immune and heart functions, respectively. We investigated the acute effects of 2,2′,6-trichlorinated biphenyl (PCB19), an NDL-PCB, on the currents of human Kv1.3 and Kv1.5 channels. PCB19 acutely blocked the Kv1.3 peak currents concentration-dependently with an IC50 of ~2 μM, without changing the steady-state current. The PCB19-induced inhibition of the Kv1.3 peak current occurred rapidly and voltage-independently, and the effect was irreversible, excluding the possibility of genomic regulation. PCB19 increased the time constants of both activation and inactivation of Kv1.3 channels, resulting in the slowing down of both ultra-rapid activation and intrinsic inactivation. However, PCB19 failed to alter the steady-state curves of activation and inactivation. Regarding the Kv1.5 channel, PCB19 affected neither the peak current nor the steady-state current at the same concentrations tested in the Kv1.3 experiments, showing selective inhibition of PCB19 on the Kv1.3 than the Kv1.5. The presented data indicate that PCB19 could acutely affect the human Kv1.3 channel through a non-genomic mechanism, possibly causing toxic effects on various human physiological functions related to the Kv1.3 channel, such as immune and neural systems. •PCB19 acutely inhibited amplitude of human Kv1.3 peak current.•Block of Kv1.3 by PCB19 was voltage-independent and irreversible.•PCB19 increased time constants of steady-state activation and inactivation of Kv1.3.•PCB19 didn't affect amplitudes of peak or steady-state currents of human Kv1.5.