Inorganic mercury and methylmercury inhibit the Cav3.1 channel expressed in human embryonic kidney 293 cells by different mechanisms.
Part of the neurotoxic effects of inorganic mercury (Hg(2+)) 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 Hg(2+) and MeHg on neuronal Ca(v)3.1 (T-type) calcium channel stably expressed in the human embryonic kidney (HEK) 293 cell line. Hg(2+) acutely inhibited current through the Ca(v)3.1 calcium channel in concentrations 10 nM and higher with an IC(50) of 0.63 +/- 0.11 microM 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 microM Hg(2+). MeHg in concentrations between 10 nM and 100 microM inhibited the current through the Ca(v)3.1 calcium channel with an IC(50) of 13.0 +/- 5.0 microM 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 Hg(2+) or MeHg did not affect HEK 293 cell viability. In conclusion, interaction with the Ca(v)3.1 calcium channel may significantly contribute to neuronal symptoms of mercury poisoning during both acute poisoning and long-term environmental exposure.
Tarabová
Bohumila
B
Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Bratislava.
Kurejová
Martina
M
Sulová
Zdena
Z
Drabová
Melinda
M
Lacinová
L'ubica
L
D017209:Apoptosis / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000633:toxicity*; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D017669:Mercury Compounds / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000633:toxicity*
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D017669:Mercury Compounds; D008767:Methylmercury Compounds