A MOLECULAR DETERMINANT FOR SUBMILLISECOND DESENSITIZATION IN GLUTAMATE RECEPTORS

The decay of excitatory postsynaptic currents in central neurons media ted by ha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) recep tors is likely to be shaped either by receptor desensitization or by o ffset after removal of glutamate from the synaptic cleft. Native AMPA receptors show desensitization time constants of 1 to about 10 millise conds, but the underlying molecular determinants of these large differ ences are unknown. Cloned AMPA receptors carrying the ''flop'' splice variants of glutamate receptor subtype C (GluR-C) and GluR-D are shown to have desensitization time constants of around 1 millisecond, where as those with the ''flip'' variants are about four ti mes slower. Cere bellar granule cells switch their expression of GluR-D splice variants from mostly flip forms in early stages to predominantly flop forms in the adult rat brain. These findings suggest that rapid desensitizatio n of AM PA receptors can be regulated by the expression and alternativ e splicing of GluR-D gene transcripts.