Na+ channel-mediated Ca2+ entry leads to glutamate secretion in mouse neocortical preplate.
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.
Platel
J-C
JC
Laboratoire Canaux Ioniques et Signalisation, Institut National de la Santé et de la Recherche Médicale E9931, Département de Réponse et Dynamique Cellulaires-Commissariat à l'Energie Atomique, Université Joseph Fourier, Grenoble, France.
Boisseau
S
S
Dupuis
A
A
Brocard
J
J
Poupard
A
A
Savasta
M
M
Villaz
M
M
Albrieux
M
M
D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D005089:Exocytosis; D018698:Glutamic Acid / Q000378:metabolism*; D005998:Glycine / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D016202:N-Methylaspartate / Q000737:chemistry; D019579:Neocortex / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D018009:Receptors, Glycine / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry; D012964:Sodium / Q000737:chemistry* / Q000378:metabolism; D015222:Sodium Channels / Q000737:chemistry*; D012984:Software; D013654:Taurine / Q000737:chemistry; D013997:Time Factors; D014701:Veratridine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018091:Receptors, AMPA; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D015222:Sodium Channels; D013654:Taurine; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D014701:Veratridine; D012964:Sodium; D002118:Calcium; D005998:Glycine