What is the significance of the NMDA receptor?

• A. It has no voltage dependence and is activated solely by ligand binding.
• B. It requires both glutamate and depolarization to relieve Mg2+ block, allowing Ca2+ influx.
• C. It conducts only Na+ ions.
• D. It is blocked by magnesium at all membrane potentials.

Answer: (B)

The NMDA receptor acts as a coincidence detector in synaptic signaling: it requires both glutamate binding and a depolarized postsynaptic membrane to function. At resting potential, Mg2+ sits in the channel and blocks ion flow even when glutamate is present. When the cell depolarizes, Mg2+ is expelled, opening the channel and allowing Ca2+ (and Na+) to enter. The Ca2+ influx triggers intracellular signaling cascades that drive synaptic plasticity, such as long-term potentiation and long-term depression, which are essential for learning and memory. This dual gating—the need for glutamate and for depolarization—explains why NMDA receptors are so important: they couple presynaptic activity with postsynaptic voltage changes to enable Ca2+-mediated signaling. The other statements don’t fit because the receptor is not activated solely by ligand binding (it has voltage dependence due to Mg2+), it is not limited to Na+ (Ca2+ permeability is a key feature), and Mg2+ blocks it only atresting potentials, not at all membrane potentials.