NMDA RECEPTOR DIVERSITY IN THE CEREBELLUM - IDENTIFICATION OF SUBUNITS CONTRIBUTING TO FUNCTIONAL RECEPTORS

Recent studies of N-methyl-D-aspartate (NMDA) receptors have led to th e suggestion that there are two distinct classes of native NMDA recept ors, identifiable from their single-channel conductance properties. 'H igh-conductance' openings arise from NR2A- or NR2B-containing receptor s, and 'low-conductance' openings arise from NR2C- or NR2D-containing receptors. In addition, the low-conductance channels show reduced sens itivity to block by Mg2+. The readily identified cell types and simple architecture of the cerebellum make it an ideal model system in which to determine the contribution of specific subunits to functional NMDA receptors. Furthermore, mRNA for all of these four NR2 subunits are r epresented in this brain region. We have examined NMDA channels in Pur kinje cells, deep cerebellar nuclei (DCN) neurons and Golgi cells. Fir st we find that NR2D-containing NMDA. receptors give rise to low-condu ctance openings in cell-attached recordings from Purkinje cells. The c haracteristic conductance of these events cannot, therefore, be ascrib ed to patch excision. Second, patches from some DCN neurons exhibit mi xed populations of high- and low-conductance openings. Third, Golgi ce lls also exhibit a mixed population of high- and low-conductance NMDA receptor openings. The features of these low-conductance openings are consistent with the presence of NR2D-containing NMDA receptors, as sug gested by in situ hybridization data. On the other hand the existence of high-conductance channels, with properties typical of NR2B-containi ng receptors, was not expected. Our results provide new evidence about the subunit composition of NMDA receptors in identified cerebellar ce lls, and suggest that examination of single-channel properties is a po tentially powerful approach for determining the possible subunit compo sition of native NMDA receptors. (C) 1998 Elsevier Science Ltd. All ri ghts reserved.