Calcium-dependent inactivation of synaptic NMDA receptors in hippocampal neurons

C. Rosenmund, A. Feltz, G. L. Westbrook

Research output: Contribution to journalArticle

141 Scopus citations

Abstract

1. We examined whether synaptically activated N-methyl-D-aspartate (NMDA) receptors are regulated by intracellular calcium in cultured hippocampal neurons by comparing excitatory postsynaptic currents (EPSCs) to the previously described calcium-dependent regulation of whole cell NMDA currents. Standard whole cell recording and fast application methods were used. 2. Low-frequency (0.2 Hz) stimulation of EPSCs in the presence of 2- amino-5-phosphonovalerate (AP5) evoked a constant amplitude α-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor mediated EPSC. On removal of AP5 in Ca2+containing solutions, the amplitude of the slow NMDA receptor-mediated EPSC decreased by ~50% during the next 10 stimuli. The decrease in the EPSC was dependent on the extracellular calcium concentration and stimulus frequency, consistent with Ca2+-dependent desensitization/inactivation of postsynaptic NMDA receptors. A whole cell prepulse of NMDA (10 μM, 10 s) in Ca2+-containing solutions inhibited the slow EPSC to a similar degree. A series of slow EPSCs also produced Ca2+- dependent inactivation of whole cell NMDA currents evoked in low calcium solutions. 3. These results demonstrate that synaptic NMDA receptors are inactivated by intracellular calcium and that calcium entry through synaptically activated NMDA receptors is sufficient to provide feedback inhibition of the slow EPSC.

Original languageEnglish (US)
Pages (from-to)427-430
Number of pages4
JournalJournal of neurophysiology
Volume73
Issue number1
DOIs
StatePublished - 1995

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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