Activation Mechanisms of the NMDA Receptor

NMDA receptors (NMDARs) are glutamate-gated cation channels with high calcium permeability that play important roles in many aspects of the biology of higher organisms. They are critical for the development of the central nervous system (CNS), generation of rhythms for breathing and locomotion, and the processes underlying learning, memory, and neuroplasticity. Consequently, abnormal expression levels and altered NMDAR function have been implicated in numerous neurological disorders and pathological conditions. NMDAR hypofunction can result in cognitive defects, whereas overstimulation causes excitotoxicity and subsequent neurodegeneration. Therefore, NMDARs are important therapeutic targets for many CNS disorders1-8 including stroke, hypoxia, ischemia, head trauma, Huntington’s, Parkinson’s, and Alzheimer’s13.1 Introduction ... 283 13.2 Function of NMDA Receptors ...284