A calcium-dependent feedback mechanism participates in shaping single NMDAminiature EPSCs

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