Voltage-dependent kinetics of N-methyl-D-aspartate synaptic currents in rat cerebellar granule cells

Abstract

Decay kinetics of N-methyl-D-aspartate excitatory postsynaptic currents (NMDA-EPSCs) have been voltage-dependent in some, but not all neurons studied so far, and almost no information has been available on the voltage-dependence of the rising phase. In this work we investigated the effect of membrane potential on rising and decay kinetics of the NMDA-EPSC in cerebellar granule cells using the tight-seal whole-cell recording technique. NMDA-EPSCs were evoked by electrical mossy fibre stimulation in the presence of 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione, 1.2 mM Mg2+ and 5 microM glycine. The rate of rise of NMDA-EPSCs remained substantially unchanged when the cell was depolarized, indicating that the limiting step of channel opening was voltage-insensitive. The NMDA-EPSC, however, flattened around the peak and the time-to-peak increased. This observation was explained by the influence of decay. Decay was biphasic and slowed down with membrane depolarization. Moreover, the fast component of decay increased less than the slow component. This complex voltage-dependence may extend the integrative role of the NMDA current during synaptic transmission.