Na+ channel-mediated Ca2+ entry leads to glutamate secretion in mouse neocortical preplate. - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2005

Na+ channel-mediated Ca2+ entry leads to glutamate secretion in mouse neocortical preplate.

Résumé

Before synaptogenesis, early excitability implicating voltage-dependent and transmitter-activated channels is known to be crucial for neuronal development. We previously showed that preplate (PP) neurons of the mouse neocortex express functional Na(+) channels as early as embryonic day 12. In this study, we investigated the role of these Na(+) channels in signaling during early development. In the neocortex of embryonic-day-13 mice, activation of Na(+) channels with veratridine induced a large Ca(2+) response throughout the neocortex, even in cell populations that lack the Na(+) channel. This Na(+)-dependent Ca(2+) activity requires external Ca(2+) and is completely blocked by inhibitors of Na(+)/Ca(2+) exchangers. Moreover, veratridine-induced Ca(2+) increase coincides with a burst of exocytosis in the PP. In parallel, we show that Na(+) channel stimulation enhances glutamate secretion in the neocortical wall. Released glutamate triggers further Ca(2+) response in PP and ventricular zone, as indicated by the decreased response to veratridine in the presence of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor and NMDA-receptor inhibitors. Therefore, the combined activation of the Na(+) channel and the Na(+)/Ca(2+) exchanger triggers Ca(2+) signaling in the PP neurons, leading to glutamate secretion, which amplifies the signal and serves as an autocrine/paracrine transmitter before functional synapses are formed in the neocortex. Membrane depolarization induced by glycine receptors activation could be one physiological activator of this Na(+) channel-dependent pathway.
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Dates et versions

inserm-00412503 , version 1 (17-11-2009)

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Jean-Claude Platel, Sylvie Boisseau, Alain Dupuis, Jacques S. Brocard, Annie Poupard, et al.. Na+ channel-mediated Ca2+ entry leads to glutamate secretion in mouse neocortical preplate.. Proceedings of the National Academy of Sciences of the United States of America, 2005, 102 (52), pp.19174-9. ⟨10.1073/pnas.0504540102⟩. ⟨inserm-00412503⟩
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