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Calcium-dependent inactivation of the monosynaptic NMDA EPSCs in rat hippocampal neurons in culture.

Igor Medina 1 Xavier Leinekugel 1 yehezkel Ben-Ari 1, * 
* Corresponding author
Abstract : The effects of increased dendritic calcium concentration ([Ca2+]i) induced by single action potentials on monosynaptic glutamatergic excitatory postsynaptic currents (EPSCs) were studied in cultured rat hippocampal neurons. To investigate the respective roles of pre- and postsynaptic elements in the depolarization-induced NMDAR inactivation, we have performed simultaneous paired whole-cell recordings from monosynaptically connected pre- and postsynaptic hippocampal neurons. We report that the single firing of the postsynaptic neuron did not result in inactivation of the NMDAR-EPSC, whereas a burst of depolarizing steps transiently depressed the NMDAR-EPSCs in both pyramidal cells and interneurons. This effect was mediated by postsynaptic voltage-gated Ca2+ influx, as it was prevented by: (i) buffering postsynaptic [Ca2+]i with 30 mM BAPTA; (ii) removing extracellular Ca2+; or (iii) applying Cd2+o (100 microM), a voltage-gated calcium channel blocker. It does not involve presynaptic mechanisms as it selectively affected NMDA but not alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor-mediated EPSCs. These results suggest that inactivation of NMDAR-channels by voltage-gated Ca influx is a general property of hippocampal neurons, which may play an important role in reducing postsynaptic NMDAR Ca2+ influx that leads to plasticity or excitotoxicity during sustained neuronal activity.
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  • HAL Id : inserm-00486121, version 1
  • PUBMED : 10383632



Igor Medina, Xavier Leinekugel, yehezkel Ben-Ari. Calcium-dependent inactivation of the monosynaptic NMDA EPSCs in rat hippocampal neurons in culture.. European Journal of Neuroscience, Wiley, 1999, 11 (7), pp.2422-30. ⟨inserm-00486121⟩



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