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-incluced 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. (C) 2001 Lippincott Williams & Wilkins.