Glutamate Receptors

Question 1

Define a Glutamate receptor.

Answer 1

• Glutamate is a fast acting excitatory neurotransmitter in the CNS while their receptors are excitatory ionotropic receptors.
• They are ligand gated ion channels which are essential for brain development and function.
• They all share the same basic structure, beginning at the N terminus (extracellular) followed by the ligand binding domain, the 4 transmembrane domains finally the C terminus (intracellular).
• Receptors play an important role in excitatory synaptic transmissions, the process in which neurons communicate.
• An electrical impulse causes an influx of Ca2+ which causes the release of chemical NT glutamate.
• The glutamate receptors bind glutamate, charged ions such as Na+ and Ca2+ pass through a channel in the centre of the receptor complex

Question 2

Describe a NMDA receptor.

Answer 2

• Consists of GluN1 and GluN2 subunits, the N1 is an essential component while the N2 varies from A-D to generate different variations.
• They function as a modulator of synaptic responses, they are inactive at resting potentials due to a voltage dependent block caused by Mg2+ preventing ion flow.
• Sustained activity of AMPA receptors depolarises post-synaptic cell releasing inhibition and activating the receptor.
• Unlike GluA2 containing AMPA receptors, NMDA receptors are permeable to calcium ions and lead to an influx into post synaptic cell upon activation.

Question 3

Describe AMPA receptors.

Answer 3

• AMPA receptors mediate fast synaptic transmissions in the CNS and are composed of subunits GluA1-4.
• The ligand binding domain is made up of N terminal region S1 and S2.
• The lack of calcium permeability is caused by a change in the transmembrane 2 region. The protein glutamine (Q) is mutated to arginine (R) in the GluA2.
• The insertion of Ca2+ permeable AMPA could potentially increase channel conductance.