ABSTRACT
The N-methyl-D-aspartate (NMDA) subtypes of glutamate receptors are intimately involved in a number of important neuronal activities in mammalian nervous systems including neuronal migration, synaptogenesis, neuronal plasticity, neuronal survival, and excitotoxicity. Through these activities, NMDA receptors (NRs) play an important role in the development of drug addiction, pain perception, and the pathogenesis of neurological disorders such as schizophrenia and Huntington’s disease.1-10
It is generally believed that aberrant or pathological NR effects occur mainly via abnormal receptor activity, resulting from altered availability of agonists or modied quality or quantity of membrane-associated receptors. In mammals, functional NRs are heterotetramers of subunits encoded by three gene families, i.e., NMDAR1 (NR1 or Grin1), NMDAR2 (NR2 or Grin2), and NMDAR3 (NR3 or Grin3).3,4,11 The NR1 family has one gene; the NR2 family has four (designated A through D); and the NR3 family has two (A and B). Structurally, NR1 is an essential component found in all tetramers, while different NR2 members are incorporated based on age and nervous system region. NR3 proteins function as negative components when included in the structures.3,4,11,12 Eight variants of NR1 protein are produced by alternative splicing and distributed differentially in nervous systems.13-15 This complex composition of different subunits and splicing variants forms the primary basis of the functional diversity of NRs.
