Subunit interactions and AMPA receptor desensitization

Most AMPA-type glutamate receptors (GluRs) exhibit rapid and virtually comp lete desensitization when activated by glutamate, and at some central synap ses it is largely desensitization that determines the decay of EPSCs. Howev er, the mechanisms underlying the conformation change that results in desen sitization are not fully understood. AMPA receptor subunits that contain a single amino acid substitution have been shown to form homomeric channels t hat show markedly reduced desensitization. We show here that the coexpressi on of wild-type GluR1 with one such mutant, GluR1( L497Y), results in heter omeric channels that show desensitization behavior that is intermediate bet ween wild-type and mutant homomers. The relative amplitudes of the multiple exponential components present in the decay of glutamate-evoked currents d epended on the relative abundance of wild-type and mutant subunits and were described by the combinatorial distribution of the two types of subunits i nto tetrameric, but not pentameric, assemblies. Our results are consistent with recent structural data suggesting that AMPA receptors are tetrameric a ssemblies composed of two dimers.