NMDA receptors are considered 'coincidence detectors.' Which two simultaneous conditions are required to relieve the Mg²⁺ block and allow ionic current through the NMDA receptor channel?

• A Simultaneous binding of glutamate AND glycine (co-agonist), independent of membrane potential
• B Binding of GABA to NMDA receptor AND activation of metabotropic glutamate receptors
• C Hyperpolarization of the postsynaptic membrane AND simultaneous glutamate binding
• D Binding of glutamate to NMDA receptor AND postsynaptic membrane depolarization (to remove Mg²⁺ block from the channel pore) ✓

Explanation

NMDA receptors require dual conditions for activation: (1) glutamate must bind (along with the co-agonist glycine at the GluN1 subunit) to open the gate, and (2) the postsynaptic membrane must be depolarized to ~–40 mV or above to electrically repel the Mg²⁺ ion that otherwise occludes the channel pore at resting potential. This voltage-dependent Mg²⁺ block is why NMDA receptors act as coincidence detectors of presynaptic activity (glutamate release) and postsynaptic depolarization (prior AMPA-mediated EPSPs). Ca²⁺ influx through activated NMDA receptors triggers LTP, which is the cellular basis of learning and memory.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.