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

Abstract : 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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Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2005, 102 (52), pp.19174-9. 〈10.1073/pnas.0504540102〉
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Jean-Claude Platel, Sylvie Boisseau, Alain Dupuis, Jacques 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 , National Academy of Sciences, 2005, 102 (52), pp.19174-9. 〈10.1073/pnas.0504540102〉. 〈inserm-00412503〉

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