Molecular determinants controlling functional properties of AMPARs and NMDARs in the mammalian CNS

L-a-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs) are the two major types of postsynaptic glutamate receptors (GluRs) that mediate excitatory synaptic transmission in the mammalian central nervous system (CNS). Both AMPARs and NMDARs are multimeric proteins, probably tetramers, formed by a variety of molecularly distinct subunits. AMPARs can be assembled from four types of subunits, termed GIuR-A, -B, -C, and -D (or, in an alternative nomenclature, G1uR1, G1uR2, GluR3, and G1uR4). Additional molecular diversity of AMPARs is generated by alternative splicing of the flip-flop module and RNA editing at the Q/R and R/G site. NMDARs are heteromers primarily assembled from NR1 subunits and NR2A, B, C, or D subunits. Various splice variants have been identified for the NR1 subunit, and a new NR3 subunit has been discovered recently. Considering all combinatorial possibilities, the molecular diversity of glutamate-receptor channels is considerable (HOLLMANN, this volume).