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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on December 2, 2005; DOI: 10.1124/jpet.105.095463

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Received for publication September 9, 2005.
Revised November 21, 2005.
Accepted for publication November 30, 2005.

Inorganic mercury and methylmercury inhibit the Cav3.1 channel expressed in HEK 293 cells by different mechanisms

Bohumila Tarabova 1, Martina Kurejova 1, Zdena Sulova 1, Melinda Drabova 1, Lubica Lacinova 2*

1 Institute of Molecular Physiology and Genetics 2 Institute for Molecular Physiology and Genetics

* Address correspondence to: E-mail: lubica.lacinova{at}savba.sk

Abstract

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 Cav3.1 (T-type) calcium channel stably expressed in HEK 293 cell line. Hg2+ acutely inhibited current through the Cav3.1 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 it's peak was shifted to a more depolarized membrane potentials by 1 µM of Hg2+. MeHg in concentrations between 10 nM and 100 µM inhibited the current through the Cav3.1 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 hours exposure to 10 nM MeHg had no significant effect on current amplitude, while 72 hours 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 Cav3.1 calcium channel may significantly contribute to neuronal symptoms of mercury poisoning during both acute poisoning and long-term environmental exposure.


Key words: Cav3.1, T-type calcium channel, low voltage activated, mercury, methylmercury, neurotoxicity


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