Ca2+ entry pathways in mouse spinal motor neurons in culture following in vitro exposure to methylmercury
| Autor: | Gunasekaran Ramanathan, William D. Atchison |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Time Factors
Calcium Channels L-Type AMPA receptor Toxicology Receptors N-Methyl-D-Aspartate Article Mice chemistry.chemical_compound Calcium Channels N-Type Animals Channel blocker Calcium Signaling Cells Cultured Chelating Agents Motor Neurons Dose-Response Relationship Drug Voltage-dependent calcium channel General Neuroscience Methylmercury Compounds Calcium Channel Blockers EGTA Spinal Nerves Animals Newborn chemistry Biochemistry Tetrodotoxin CNQX Biophysics Excitatory postsynaptic potential NMDA receptor Environmental Pollutants Cytophotometry Excitatory Amino Acid Antagonists Sodium Channel Blockers |
| Zdroj: | NeuroToxicology. 32:742-750 |
| ISSN: | 0161-813X |
| DOI: | 10.1016/j.neuro.2011.07.007 |
| Popis: | Methylmercury (MeHg) is a widespread environmental toxicant with major actions on the central nervous system. Among the neurons reportedly affected in cases of Hg poisoning are motor neurons; however, the direct cellular effects of MeHg on motor neurons have not been reported. Ratiometric fluorescence imaging, using the Ca(2+)-sensitive fluorophore fura-2, was used to examine the effect of MeHg on Ca(2+) homeostasis in primary cultures of mouse spinal motor neurons. In vitro MeHg exposure at concentrations (0.1-2 μM) known to affect other neurons in culture differentially, induced a biphasic rise in fura-2 fluorescence ratio indicating an increase in [Ca(2+)](i). The time-to-onset of these fura-2 fluorescence ratio changes was inversely correlated with MeHg concentration. TPEN (20 μM), a non-Ca(2+), divalent cation chelator, reduced the amplitude of the increase in fura-2 fluorescence induced by MeHg in the first phase, indicating that both Ca(2+) and non-Ca(2+) divalent cations contribute to the MeHg-induced effect. When examining various Ca(2+) entry pathways as possible targets contributing to Ca(2+) influx, we found that excitatory amino acid receptor blockers MK-801 (15 μM), and AP-5 (100 μM)-both NMDA receptor-operated ion channel blockers, CNQX (20 μM), a non-NMDA receptor blocker, and the voltage-dependent Ca(2+) channel blockers nifedipine (1 μM) and ω-conotoxin-GVIA (1 μM) all significantly delayed the development of increased Ca(2+) caused by MeHg. The voltage-dependent Na(+) channel blocker tetrodotoxin (TTX, 1 μM) did not alter the MeHg-induced increases in fura-2 fluorescence ratio. Thus, MeHg alters Ca(2+) homeostasis in mouse spinal motor neurons through excitatory amino acid receptor-mediated pathways, and nifedipine and ω-conotoxin-GVIA-sensitive pathways. Spinal motor neurons are highly sensitive to this effect of acute exposure to MeHg. |
| Databáze: | OpenAIRE |
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