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This Article Full Text Full Text (PDF) Supplemental data All Versions of this Article: 577/1/141    most recent jphysiol.2006.118026v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Carlier, E. Articles by Debanne, D. Search for Related Content PubMed PubMed Citation Articles by Carlier, E. Articles by Debanne, D. Related Collections Neuroscience

¹ INSERM U641, Marseille, F-13916 France
² Université de la Méditerranée, Faculté de médecine secteur nord, IFR 11, Marseille, F-13916 France

Brain sodium channels (NaChs) are regulated by various neurotransmitters such as acetylcholine, serotonin and dopamine. However, it is not known whether NaCh activity is regulated by glutamate, the principal brain neurotransmitter. We show here that activation of metabotropic glutamate receptor (mGluR) subtype 1 regulates fast transient (I_NaT) and persistent Na⁺ currents (I_NaP) in cortical pyramidal neurons. A selective agonist of group I mGluR, (S)-3,5-dihydroxyphenylglycine (DHPG), reduced action potential amplitude and decreased I_NaT. This reduction was blocked when DHPG was applied in the presence of selective mGluR1 antagonists. The DHPG-induced reduction of the current was accompanied by a shift of both the inactivation curve of I_NaT and the activation curve of I_NaP. These effects were dependent on the activation of PKC. The respective role of these two regulatory processes on neuronal excitability was determined by simulating transient and persistent Na⁺ conductances (G_NaT and G_NaP) with fast dynamic-clamp techniques. The facilitated activation of G_NaP increased excitability near the threshold, but, when combined with the down-regulation of G_NaT, repetitive firing was strongly decreased. Consistent with this finding, the mGluR1 antagonist LY367385 increased neuronal excitability when glutamatergic synaptic activity was stimulated with high external K⁺. We conclude that mGluR1-dependent regulation of Na⁺ current depresses neuronal excitability, which thus might constitute a novel mechanism of homeostatic regulation acting during intense glutamatergic synaptic activity.

(Received 27 July 2006; accepted after revision 22 August 2006; first published online 24 August 2006)
Corresponding author D. Debanne: Université de la Méditerranée, Faculté de médecine secteur nord, IFR 11, Marseille, F-13916 France. Email: debanne.d{at}jean-roche.univ-mrs.fr

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