The NMDA receptor gating machine: Lessons from single channels

The slow component of the excitatory postsynaptic current in the central nervous system is generated by the activity of NMDA receptors. The activation properties of this class of glutamate receptor determine key features of the synaptic response and have important consequences for synaptic plasticity and cell physiology. NMDA receptor activation is complex and involves ligand binding, protein conformational changes, and channel blockade. Recently, two groups have proposed state models that encapsulate the essential features of NMDA receptor gating conformational changes. These models provide insight into the NMDA receptor as a molecular machine and should help us understand and manipulate NMDA receptor-mediated synaptic function and pathologies.