We have investigated the site of expression of the potentiation of excitatory postsynaptic currents (EPSCs) induced by the activation of postsynaptic voltage-sensitive Ca2+ channels, by examining the effect of depolarizing pulses on miniature (m) EPSCs and responses to AMPA. Application of voltage pulses caused a approximately 2.5-fold increase in the mean amplitude of mEPSCs. This NMDA receptor-independent potentiation of mEPSC amplitudes was transient, returning to control values within 30-40 min. The potentiation was associated with a decrease in the number of small amplitude events and an increase in the number, as well as the maximum amplitude, of the larger events, with no apparent change in mEPSC kinetics. Accompanying the increase in mEPSC amplitudes, there was a 1.6-fold increase in the apparent frequency of events. Voltage pulse-induced potentiation was completely blocked by the inclusion of the Ca2+ chelator BAPTA in the recording pipette. Responses to repeated applications of AMPA were also potentiated following the application of voltage pulses, and the time course of this potentiation was similar to that observed with the mEPSCs. Our data indicate that rises in intracellular Ca2+ that occur independently of NMDA receptor activation can result in a potentiation of quantal size, which is due to an increase in the postsynaptic sensitivity of non-NMDA receptors.