Kinetic models for activation and modulation of NMDA receptor subtypes

•Kinetic schemes developed for NMDA receptors encapsulate their reaction mechanism.•NMDA receptor isoforms have conserved gating reactions but distinct kinetics.•Allosteric modulators or mutations alter rate constants but not gating sequence.•Presently, the goal is to unify kinetic and structural models of receptor gating. NMDA receptors are a diverse family of excitatory channels with critical roles in central synaptic transmission, development, and plasticity. Controlled expression of seven subunits and their combinatorial assembly into tetrameric receptors produces a range of molecularly distinct receptor subtypes. Despite relatively similar atomic structures, each subtype has input–output functions with unique biophysical and pharmacologic profiles. Here, we briefly summarize recent advances in understanding how gating and allosteric modulation are similar or distinct across NMDA receptor isoforms and identify open questions that will focus research in this area going forward.