Mutation of a glutamate receptor motif reveals its role in gating and δ2 receptor channel properties

Despite its importance in the cerebellum, the functions of the orphan glutamate receptor delta 2 are unknown. We examined a mutant delta 2 receptor channel in lurcher mice that was constitutively active in the absence of ligand. Because this mutation was within a highly conserved motif (YTANLAAF), we tested its effect on several glutamate receptors. Mutant delta 2 receptors showed distinct channel properties, including double rectification of the current-voltage relationship, sensitivity to a polyamine antagonist and moderate Ca2+ permeability, whereas other constitutively active mutant glutamate channels resembled wildtype channels in these respects. Moreover, the kinetics of ligand-activated currents were strikingly altered. We conclude that the delta 2 receptor has a functional ion channel pore similar to that of glutamate receptors. The motif may have a role in the channel gating of glutamate receptors.