What is the Difference Between AMPA and NMDA Receptors

The main difference between AMPA and NMDA is that only the sodium and potassium influx occur in AMPA receptors whereas, in NMDA receptors, calcium influx occurs in addition to sodium and potassium influx. Furthermore, AMPA receptors do not contain a magnesium ion block while NMDA contains a magnesium ion block in the core.  

AMPA and NMDA are two types of ionotropic, glutamate receptors. They are nonselective, ligand-gated ion channels, which mainly allow the passage of sodium and potassium ions. Moreover, glutamate is a neurotransmitter, which generates excitatory postsynaptic signals throughout the central nervous system. 

Key Areas Covered 

1. What are AMPA Receptors
     – Definition, Structure, Function
2. What are NMDA Receptors
     – Definition, Structure, Function
3. What are the Similarities Between AMPA and NMDA Receptors
     – Outline of Common Features
4. What is the Difference Between AMPA and NMDA Receptors
     – Comparison of Key Differences

Key Terms 

Agonist, AMPA Receptors, Calcium, NMDA Receptors, Potassium, Sodium 

What are AMPA Receptors 

AMPA (α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate) receptors are a type of glutamate receptors responsible for mediating the fast, synaptic transmission in the central nervous system. The AMPA receptor consists of four subunits, GluA1-4. Furthermore, the GluA2 subunit is not permeable to calcium ions since it contains arginine in the TMII region. (GluA2(R)) form.  

Figure 1: AMPA Receptor

Besides, AMPA receptors are involved in the transmission of the bulk of the fast, excitatory synaptic signals. The intensity of the post-synaptic response depends on the number of receptors at the post-synaptic surface. The type of agonist which activates the AMPA receptors is α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid. Moreover, the activation of the AMPA receptor results in nonselective transport of cations like sodium and potassium ions into the cell. And, this generates an action potential in the post-synaptic membrane. 

What are NMDA Receptors 

NMDA (N-methyl-d-aspartate) receptors are another type of glutamate receptors found in the post-synaptic membrane. The NMDA receptor is made up of two types of subunits: GluN1 and GluN2. The GluN1 subunit is essential for the function of the receptor. And, this subunit can associate with one of the four types of GluN2 subunits, GluN2A-D.  

Figure 2: NMDA Receptor

Besides, the main function of the NMDA receptors is to modulate the synaptic response. However, at the resting membrane potential, these receptors are inactive due to the presence of a magnesium block. For instance, the agonist of the NMDA receptor is N-methyl-d-aspartic acid. L-glutamate, as well as glycine, can bind to the receptor to activate it. Upon activation, NMDA receptors allow the influx of calcium along with the sodium and potassium influx. 

Similarities Between AMPA and NMDA Receptors 

• AMPA, NMDA, and, kainate receptors are the three types of glutamate receptors. 
• They are ligand-gated ion channels, which allow passing sodium and potassium ions.  
• Their names are due to the type of agonist which activates the receptor. 
• Furthermore, the activation of these receptors produces the excitatory postsynaptic responses (ESPSs).  
• Also, several protein subunits connect together to form these receptors.  

Difference Between AMPA and NMDA Receptors 

Definition 

AMPA receptors refer to a type of glutamate receptor that participates in excitatory neurotransmission and also binds α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and acts as a cation channel. Whereas, the NMDA receptors refer to a type of glutamate receptor that participates in excitatory neurotransmission and also binds N-methyl-D-aspartate. Thus, this is the main difference between AMPA and NMDA receptors.

Subunits 

Moreover, AMPA receptors consist of four subunits, GluA1-4 while NMDA receptors consist of a GluN1 subunit associated with one of the four GluN2 receptors, GluN2A-D. 

Activated by 

Activation is also a difference between AMPA and NMDA receptors. AMPA receptors are only activated by glutamate while NMDA receptors are activated by different agonists including glutamate. 

Agonist 

Furthermore, the agonist for AMPA receptor is α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid while the agonist for the NMDA receptor is N-methyl-d-aspartic acid. 

Ion Influx 

Besides, ion influx is also an important difference between AMPA and NMDA receptors. Activation of AMPA receptors results in the sodium and potassium influx while the activation of NMDA receptors results in sodium, potassium, and calcium influx. 

Magnesium Ion Block 

Another difference between AMPA and NMDA receptors is that the AMPA receptors do not contain a magnesium ion while the NMDA receptors contain magnesium receptors.  

Role  

Also, AMPA receptors are responsible for the transmission of the bulk of the fast, excitatory synaptic signals while NMDA receptors are responsible for the modulation of the synaptic response. 

Conclusion 

AMPA receptors are a type of glutamate receptors whose activation results in the influx of sodium and potassium ions. On the other hand, NMDA receptors are another type of glutamate receptor whose activation results in the influx of calcium ions in addition to the sodium and potassium ions. Therefore, the main difference between AMPA and NMDA receptors is the type of ion influx.  

References:

1. Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001. Glutamate Receptors. 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