FUNCTIONAL CORRELATION OF NMDA RECEPTOR EPSILON-SUBUNITS EXPRESSION WITH THE PROPERTIES OF SINGLE-CHANNEL AND SYNAPTIC CURRENTS IN THE DEVELOPING CEREBELLUM

NMDA receptor (NMDAR) subunits epsilon 1-epsilon 4 are expressed diffe rentially with respect to brain region and ontogenic period, but their functional roles still are unclear. We have compared an epsilon 1 sub unit-ablated mutant mouse with the wild-type to characterize the effec t of epsilon subunit expression on NMDAR-mediated single-channel curre nts and synaptic currents of granule cells in cerebellar slices. Singl e-channel and Western blot analyses indicated that the epsilon 2 subun it disappeared gradually during the first postnatal month in both wild -type and mutant mice. Concomitantly, the voltage-dependent Mg2+ block of NMDAR-mediated EPSCs (NMDA-EPSCs) was decreased. Throughout the de velopmental period studied, postnatal day 7-24 (P7-P24), the decay tim e course of NMDA-EPSCs in epsilon 1 mutant (-/-) mice was slower than in wild-type mice. We suggest that the expression of the epsilon 3 sub unit late in development is responsible for a reduction in the sensiti vity of NMDA-EPSCs to block by extracellular Mg2+ and that receptors c ontaining the epsilon 1 subunit determine the fast kinetics of the NMD A-EPSCs.