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.