• Neurotoxicology · Dec 2011

    Ca2+ entry pathways in mouse spinal motor neurons in culture following in vitro exposure to methylmercury.

    • Gunasekaran Ramanathan and William D Atchison.
    • Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA.
    • Neurotoxicology. 2011 Dec 1; 32 (6): 742-50.

    AbstractMethylmercury (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.Copyright © 2011 Elsevier Inc. All rights reserved.

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