Calcium-dependent inactivation of the monosynaptic NMDA EPSCs in rat hippocampal neurons in culture.
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.
Medina
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I
INSERM, UnitE 29, Hopital de PortRoyal, 123, Bd de PortRoyal, France.
Leinekugel
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X
Ben-Ari
Y
Y
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D002478:Cells, Cultured; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D013997:Time Factors
D015220:Calcium Channels; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium