NMDA treatment and K+-induced depolarization selectively promote the expression of an NMDA-preferring class of the ionotropic glutamate receptors in cerebellar granule neurones

Abstract Growth conditions which promote the survival of cerebellar granule cells in culture, such as high K + or N- methyl- d -aspartate (NMDA) treatment, also promote the functional expression of an NMDA-preferring subtype alone of the ionotropic glutamate receptors. The selective regulation of NMDA receptors detected electrophysiologically in individual cells, using the whole cell patch clamp technique, is characteristic of granule cells in general: NMDA-induced 45 Ca 2+ influx increased several-fold in cultures treated with either high K + or NMDA. The increase in NMDA receptor activity was correlated with an increase in the expression of an NMDA receptor protein. Since the effect of these ‘trophic’ conditions is mediated through Ca 2+ , the induced increase in the density of NMDA receptors (which gate a Ca 2+ conductance) provides a positive feedback for strengthening the trophic influences.