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TOXICOLOGY

Inorganic Mercury and Methylmercury Inhibit the Ca_v3.1 Channel Expressed in Human Embryonic Kidney 293 Cells by Different Mechanisms

Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Bratislava, Slovakia

Part of the neurotoxic effects of inorganic mercury (Hg²⁺) and methylmercury (MeHg) was attributed to their interaction with voltage-activated calcium channels. Effects of mercury on T-type calcium channels are controversial. Therefore, we investigated effects of Hg²⁺ and MeHg on neuronal Ca_v3.1 (T-type) calcium channel stably expressed in the human embryonic kidney (HEK) 293 cell line. Hg²⁺ acutely inhibited current through the Ca_v3.1 calcium channel in concentrations 10 nM and higher with an IC₅₀ of 0.63 ± 0.11 µM and a Hill coefficient of 0.73 ± 0.08. Inhibition was accompanied by strong deceleration of current activation, inactivation, and deactivation. The current-voltage relation was broadened, and its peak was shifted to a more depolarized membrane potentials by 1 µM Hg²⁺. MeHg in concentrations between 10 nM and 100 µM inhibited the current through the Ca_v3.1 calcium channel with an IC₅₀ of 13.0 ± 5.0 µM and a Hill coefficient of 0.47 ± 0.09. Low concentration of MeHg (10 pM to 1 nM) had both positive and negative effects on the current amplitude. Micromolar concentrations of MeHg reduced the speed of current activation and accelerated current inactivation and deactivation. The current-voltage relation was not affected. Up to 72 h of exposure to 10 nM MeHg had no significant effect on current amplitude, whereas 72-h-long exposure to 1 nM MeHg increased significantly current density. Acute treatment with Hg²⁺ or MeHg did not affect HEK 293 cell viability. In conclusion, interaction with the Ca_v3.1 calcium channel may significantly contribute to neuronal symptoms of mercury poisoning during both acute poisoning and long-term environmental exposure.

Address correspondence to: L'ubica Lacinová, Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlárska 5, 833 34 Bratislava, Slovakia. E-mail: lubica.lacinova{at}savba.sk

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