A calcium-dependent feedback mechanism participates in shaping single NMDA miniature EPSCs

J Neurosci. 2001 Jan 1;21(1):1-9. doi: 10.1523/JNEUROSCI.21-01-00001.2001.


NMDA receptors (NMDARs) are highly calcium-permeable and are negatively regulated by intracellular calcium during prolonged exposure to agonist. We have investigated whether calcium-mediated feedback occurs during transient exposure to glutamate during single synaptic events. Examination of miniature EPSCs (mEPSCs) indicated that the decay kinetics of the NMDAR component was markedly slowed by the intracellular perfusion of exogenous calcium buffers (BAPTA or Fluo-3). In contrast, the AMPA receptor component of the miniature EPSC was unaffected. Slow on-rate calcium buffers, such as EGTA, did not alter kinetics of the NMDAR component of the mEPSC. Addition of exogenous fast calcium buffers did not slow the decay kinetics of glutamate-evoked currents mediated by NR1/NR2A heteromers expressed in HEK 293 cells, suggesting that the effect we observed in neurons may be specific to processes associated with synaptically activated receptors. Trial-to-trial amplitude variability of miniature calcium transients mediated by NMDARs increased with the injection of exogenous calcium buffers, suggesting that the amplitude of synaptic calcium transients are maintained at a rather constant level by a calcium-mediated feedback mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / pharmacology
  • Animals
  • Barium / pharmacology
  • Calcineurin Inhibitors
  • Calcium / metabolism*
  • Calcium / pharmacology
  • Calcium Channels / metabolism
  • Cells, Cultured
  • Chelating Agents / pharmacology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Feedback / drug effects
  • Feedback / physiology
  • Fluorescent Dyes
  • Glutamic Acid / metabolism
  • Glutamic Acid / pharmacology
  • Humans
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • Rats
  • Reaction Time / drug effects
  • Receptors, AMPA / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Strontium / pharmacology
  • Synapses / metabolism
  • Xanthenes / pharmacology


  • Aniline Compounds
  • Calcineurin Inhibitors
  • Calcium Channels
  • Chelating Agents
  • Fluorescent Dyes
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Xanthenes
  • Fluo-3
  • Barium
  • Glutamic Acid
  • Egtazic Acid
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Calcium
  • Strontium