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Metabotropic glutamate receptor subtype 1 regulates sodium currents in rat neocortical pyramidal neurons

Abstract : Brain sodium channels (NaChs) are regulated by various neurotransmitters such as acetyl-choline, 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.
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Edmond Carlier, Valérie Sourdet, Sami Boudkkazi, Patrice Déglise, Norbert Ankri, et al.. Metabotropic glutamate receptor subtype 1 regulates sodium currents in rat neocortical pyramidal neurons. The Journal of Physiology, Wiley, 2006, 577 (1), pp.141-154. ⟨10.1113/jphysiol.2006.118026⟩. ⟨hal-01766852⟩

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