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Differential down-regulation of voltage-gated calcium channel currents by glutamate and BDNF in embryonic cortical neurons.

Abstract : In the embryonic brain, post-mitotic cortical neurons migrate from their place of origin to their final location. Various external factors such as hormones, neurotransmitters or peptides regulate their migration. To date, however, only a few studies have investigated the effects of these external factors on the electrical properties of the newly formed embryonic cortical neurons. The aim of the present study was to determine whether glutamate and brain-derived neurotrophic factor (BDNF), known to regulate neuronal cell migration, could modulate currents through voltage-gated calcium channels (ICa) in cortical neurons isolated from embryonic day 13 (E13) mouse foetuses. Whole cell recordings of ICa showed that E13 cortical cells kept 1 day in vitro expressed functional low- and high-voltage activated (LVA and HVA) Ca2+ channels of T-, L- and N-types. A 1-day glutamate treatment non-specifically inhibited LVA and HVA ICa whereas BDNF down-regulated HVA with N-type ICa being more depressed than L-type ICa. The glutamate-induced ICa inhibition was mimicked by NMDA. BDNF exerted its action by recruiting trkB receptors and SKF-96365-sensitive channels. BAPTA prevented the glutamate- and the BDNF-dependent inhibition of Ica, indicating a Ca2+-dependent mechanism of action. It is proposed that an influx of Ca2+ through NMDA receptors depresses the expression of LVA and HVA Ca2+ channels whereas a Ca2+ influx through SKF-96365-sensitive TRPC (transient receptor potential protein of C subtype) channels preferentially inhibits the expression of HVA Ca2+ channels. Glutamate and BDNF appear as potent modulators of the electrical properties of early post-mitotic neurons. By down-regulating ICa they could exert a neuroprotective action on embryonic cortical neurons.
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Alexandre Bouron, Sylvie Boisseau, Michel de Waard, Leticia Peris. Differential down-regulation of voltage-gated calcium channel currents by glutamate and BDNF in embryonic cortical neurons.. European Journal of Neuroscience, Wiley, 2006, 24 (3), pp.699-708. ⟨10.1111/j.1460-9568.2006.04946.x⟩. ⟨inserm-00380053⟩



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