Difference Between AMPA and NMDA Receptors

The key difference between AMPA and NMDA receptors is that the specific agonist of AMPA receptor is alpha-amino – 3 – hydroxyl – 5 – methyl – 4 – isoxazole propionic acid (AMPA), while the specific agonist of the NMDA receptor is N – methyl – D – aspartate (NMDA).

There are three main types of glutamate receptors. Their difference is based on the agonist that binds for the activation of the receptor for glutamate binding. Glutamate binding will open the ion gated channels for the transport of sodium and potassium ions. Also, NMDA receptors also facilitate the flux of calcium ions across the membrane.

1. Overview and Key Difference
2. What are AMPA Receptors
3. What are NMDA Receptors
4. Similarities Between AMPA and NMDA Receptors
5. Side by Side Comparison – AMPA vs NMDA Receptors in Tabular Form
6. Summary

What are AMPA Receptors?

The term AMPA receptor is the abbreviation form of alpha-amino – 3 – hydroxyl – 5 – methyl – 4 – isoxazole propionic acid receptor. This receptor is also known as AMPAR or quisqualate. It is a type of Glutamate receptor and is an ionotropic receptor. The AMPA receptor is a transmembrane receptor that penetrates the plasma membrane’s lipid bilayer. The glutamate acts as the ligand to bind to the AMPA receptor.

Difference Between AMPA and NMDA Receptors

Figure 01: AMPA Receptors

The receptor is also capable of activating AMPA, which is an agonist analogue of glutamate. Thus, the receptor gains the name AMPA receptor. Also, the receptor is widely distributed in the brain and the nervous system. It is mainly due to the active role glutamate plays in nervous coordination and signalling.

Furthermore, there are four types of subunits in the AMPA receptor. And, different genes encode each subunit. Therefore, mutations in these genes encoding the subunits may result in the malfunction of the entire receptor as a whole. Hence, the AMPA receptor is also a heterotetrameric protein. Due to this structure, glutamate or its agonists can bind to any of the four subunits for activation.

What are NMDA Receptors?

NMDA receptor is the abbreviation for N – methyl – D – aspartate receptor. It is also known as the NMDAR. NMDA receptor is a type of glutamate receptor which is ionotropic in nature. The receptor is named after the agonist that activates the receptor. NMDA receptor is a channel protein that is composed of three subunits, encoded by three genes. They are mostly distributed in the nerve cells.

The activation of the NMDA receptor for the binding of glutamate takes place in the presence of glycine or serine. This is referred to as the co-activation of the NMDA receptor. Upon binding, the entry of positive ions is initiated. The binding of the agonist NMDA is specific for the NMDA receptor.

Figure 02: NMDA Receptors

The main function of the NMDA receptor is to aid in the signal transduction process in nerve cells. Therefore, they activate depolarization by allowing Sodium and potassium ion movements. Furthermore, the role of the NMDA receptor also expands in facilitating synaptic plasticity. This is mediated by the ability of the NMDA receptor to allow Calcium ion flux.

What are the Similarities Between AMPA and NMDA Receptors?

AMPA and NMDA receptors are types of glutamate receptors.
Both are mostly present in nerve cells and facilitate nerve impulse transmission.
They are ionotropic receptors.
Both are present in the plasma membrane.
Moreover, they show high specificity.
Both can be manipulated by drugs.
Furthermore, they facilitate the movement of ions across the membrane
Both types of proteins contain multiple subunits coded by different genes.
Moreover, both are heteromeric proteins.

What is the Difference Between AMPA and NMDA Receptors?

The key difference between AMPA and NMDA receptors is based on their agonists. While AMPA receptors have alpha-amino – 3 – hydroxyl – 5 – methyl – 4 – isoxazole propionic acid as its agonist, N – methyl – D – aspartate is the agonist for the NMDA receptor. Due to this change in the type of agonist, further changes take place in the two receptors. In NMDA receptors, co-stimulation is mandatory, but it is not required for AMPA receptors. Their structures also vary based on the number of subunits each receptor possesses. AMPA receptors have four subunits, while NMDA receptors have three subunits.

The below infographic summarizes the difference between AMPA and NMDA Receptors.

Summary – AMPA vs NMDA Receptors

AMPA and NMDA are two receptors that facilitate glutamate binding. The difference between AMPA and NMDA receptors is based on the agonist each one uses for the activation of the receptor. While the AMPA receptor uses alpha-amino – 3 – hydroxyl – 5 – methyl – 4 – isoxazole propionic acid, NMDA uses N – methyl – D – aspartate as the agonist. The structure of the two receptors varies in the number of subunits each possesses. Further, the NMDA receptor requires co-stimulation of the receptor with glycine or serine, whereas AMPA receptor does not need any co-stimulation for its activation.

Reference:

1. Purves, Dale. “Glutamate Receptors.” Neuroscience. 2nd Edition., U.S. National Library of Medicine, 1 Jan. 1970, Available here.

Image Courtesy:

1. “AMPA receptor” By Curtis Neveu – Own work (CC BY-SA 3.0) via Commons Wikimedia
2. “Activated NMDAR” By RicHard-59 – Own work, based on File:Activated NMDAR.PNG (CC BY-SA 3.0) via Commons Wikimedia