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Pflugers Arch ; 465(12): 1727-40, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23821297

RESUMO

Methylmercury, a potent environmental pollutant responsible for fatal food poisoning, blocked calcium channels of bovine chromaffin cells in a time- and concentration-dependent manner with an IC50 of 0.93 µM. This blockade was not reversed upon wash-out and was greater at more depolarising holding potentials (i.e. 21 % at -110 mV and 60 % at -50 mV, after 3 min perfusion with methylmercury). In ω-toxins-sensitive calcium channels, methylmercury caused a higher blockade of I Ba than in ω-toxins-resistant ones, in which a lower blockade was detected. The sodium current was also blocked by acute application of methylmercury in a time- and concentration-dependent manner with an IC50 of 1.05 µM. The blockade was not reversed upon wash-out of the drug. The drug inhibited sodium current at all test potentials and shows a shift of the I-V curve to the left of about 10 mV. Intracellular dialysis with methylmercury caused no blockade of calcium or sodium channels. Voltage-dependent potassium current was not affected by methylmercury. Calcium- and voltage-dependent potassium current was also drastically depressed. This blockade was related to the prevention of Ca(2+) influx through voltage-dependent calcium channels coupled to BK channels. Under current-clamp conditions, the blockade of ionic current present during the generation and termination of action potentials led to a drastic alteration of cellular excitability. The application of methylmercury greatly reduced the shape and the number of electrically evoked action potentials. Taken together, these results point out that the neurotoxic action evoked by methylmercury may be associated to alteration of cellular excitability by blocking ionic currents responsible for the generation and termination of action potentials.


Assuntos
Canais de Cálcio/efeitos dos fármacos , Compostos de Metilmercúrio/farmacologia , Canais de Sódio/efeitos dos fármacos , Animais , Bário/fisiologia , Bloqueadores dos Canais de Cálcio/farmacologia , Bovinos , Células Cromafins/fisiologia , Concentração Inibidora 50 , Nifedipino/farmacologia , Técnicas de Patch-Clamp , ômega-Agatoxina IVA/farmacologia , ômega-Conotoxina GVIA/farmacologia
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