Journal
NEUROCHEMISTRY INTERNATIONAL
Volume 43, Issue 4-5, Pages 273-278Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0197-0186(03)00012-3
Keywords
Ca-45 uptake; cerebellar granule neurons; dantrolene; DMSO; NMDA receptors
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Dantrolene is an inhibitor of a skeletal muscle subtype of ryanodine receptors that stabilizes intracellular calcium concentrations and exerts neuroprotective effects in neurons submitted to excitotoxic challenges. The mechanisms of dantrolene-induced neuroprotection are not clear. In this study, using a model of cultured rat cerebellar granule neurons, we demonstrated that dantrolene inhibits NMDA-evoked Ca-45 uptake, indicating that this drug may inhibit the activity of NMDA receptor channels. Primary neuronal cultures were incubated for 10 min in Mg2+-free ionic medium with NMDA and Ca-45 in the presence of different concentrations of dantrolene, then radioactivity in neurons was measured by liquid scintillation spectroscopy. The results demonstrated that dantrolene, applied at micromolar concentrations, inhibits NMDA-evoked Ca-45 uptake in neurons in a dose-dependent manner. DMSO, a vehicle to dantrolene, in concentrations used in this study had no effect on NMDA-evoked Ca-45 uptake. These results, indicating that dantrolene inhibits activation of the NMDA receptors, might at least partially explain the mechanisms of a dantrolene-evoked protection of neurons against excitotoxicity mediated by agonists of NMDA receptors. (C) 2003 Elsevier Science Ltd. All rights reserved.
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