Repolarization of the plasma membrane shapes NMDA-induced cytosolic [Ca2+ ] transients.

After inactivation of NMDA receptors, restoration of basal cytosolic Ca2+] (Ca2+]c) is delayed. This may be caused by Ca2+ influx via reverse Na/Ca exchange or voltage-gated Ca2+ channels, and/or by Ca2+ efflux from internal stores. Monitoring of Na+]c, Ca2+]c, and plasma membrane potential in cultured cerebellar granule cells showed that repolarization of the plasma membrane and inactivation of voltage-gated Ca channels plays the most critical role in restoration of low Ca2+]c following NMDA receptor inactivation. During NMDA receptor activation, however, an Na-dependent mechanism enhanced NMDA-induced elevation in Ca2+]c. This mechanism did not involve Na,K-ATPase activation by Na+, because it operated even when Na,K-ATPase was inhibited.