K3iii: NMDA Receptor

Name

IONOTROPIC GLUTAMATE RECEPTOR of the N-Methyl-D-Aspartate subtype

Type

  • Glutamate receptor
  • Glutamate receptors are responsible for majority of excitatory neurotransmission in CNS
  • 35% of grey matter E expenditure
  • Named after N-Methyl-D-Aspartate
  • NMDA is its selective agonist
  • e. NMDA doesn’t bind any of the other glutamate receptors

Ionotropic → allows passage of Ca2+ ions

Ligand (glutamate + co-agonist glycine) & Voltage gated (Mg2+)

Location

  • Throughout CNS → brainstem + SC
  • On 2° order neurons (esp on Dorsal Horn)

Structure

  • Tetrameric protein
  • Central cation pore → at rest blocked by Mg2+
Structure

Activation

  • Requires:
    1. Binding GLUTAMATE
    2. Binding co-agonist GLYCINE
    3. Membrane depolarisation (partial by other receptors AMPA & NK on some neurons)

↓

Mg2= block released

↓

Na+, Ca2+ influx/K+ outflow

↓

Activation of protein kinase & phosphorylating enzymes

Role in CNS

Slow ESPS

Growth

Differentiation

Apoptosis

Synaptic Plasticity (Learning & Memory)

Excitotoxicity (ie pathophysiology of epilepsy, Alzheimer’s Disease)

Pain Sensitization:

  • Normally → NO activity @ NMDA receptor as membrane is not depolarised enough for Mg2+ displacement
  • Persistent pain will ↑[GLUTAMATE] & ↑signal transmission & causing Mg2+ dislodgement → NMDA receptor activates → CENTRAL SENSITISATION via 2nd messenger & further release of excitatory NT which ↑pain signal, even to benign stimuli
  • KA WIND UP

Channel Blockers

Phencyclidine

Memantidine

Ketamine

Mg++