Glutamate impairs neuronal calcium extrusion while reducing sodium gradient.

The rate of decrease of neuronal [Ca2+]i after an elevation induced by a glutamate pulse is much slower than that after a comparable [Ca2+]i elevation induced by a K+ depolarization. To investigate whether the [Na+]i increase taking place during the glutamate pulse reduces the rate of Ca2+ extrusion, we monitored simultaneously [Na+]i and [Ca2+]i during a K+ depolarization and a glutamate pulse lasting 1 min. The K+ depolarization evoked only a transient increase of [Na+]i from 4 mM to 13 mM, whereas the glutamate pulse increased [Na+]i to 60 mM, and this increase persisted after glutamate removal. An application of bepridil immediately after glutamate pulse when [Na+]i was greatly elevated, but not 14 min after glutamate removal when a basal [Na+]i was restored, evoked a [Ca2+]i increase accompanied by a decrease of [Na+]i, indicating a reverse mode of operation of the Na+/Ca2+ exchanger. These data suggest that the glutamate-evoked increase in [Na+]i may play a role in Ca2+ homeostasis destabilization.