Voltage sensitivity of NMDA-receptor mediated postsynaptic currents

Patch-clamp techniques were used to record pharmacologically-isolated N-methyl-D-aspartate-mediated excitatory postsynaptic currents (NMDA-EPSCs) from dentate granule cells in thin rat hippocampal slices. Membrane voltage modulated these EPSCs in two ways. Firstly, depolarization from resting potential enhanced EPSC amplitudes, as expected for a voltage-dependent block by Mg²⁺ of synaptically activated NMDA receptor channels. Secondly, depolarization markedly prolonged the time course of decay of NMDA-EPSCs in normal and low extracellular Mg²⁺. Both mechanisms were complementary in establishing a strong dependence between membrane potential and the amount of charge, namely Ca²⁺, transferred through synaptically activated NMDA receptor channels, that presumably underlies induction of long-term potentiation in the hippocampus.