Down-regulation of NMDA receptor activity by NMDA.

Rat cerebellar granule cells were cultured in a medium containing 25 mM KCl. The presence of NMDA during culture caused strong down-regulation of 45Ca uptake through the NMDA receptor channel. The process affected neither the viability nor the protein content of the cells. The developmental program of NMDA receptor activity was resumed after removal of NMDA from the culture medium, dependent apparently on protein synthesis. The down-regulation also rendered the neurons resistant to NMDA toxicity. It permitted replenishment of the culture with fresh medium, which is extremely toxic for cells cultured in absence of NMDA. Such down-regulation might perhaps play a role in adjusting the activity of post synaptic NMDA receptors, following synaptogenesis.