Glutamate is the main excitatory neurotransmitter in the central nervous system, or CNS, of mammals and it primarily interacts with both metabotropic and ionotropic receptors to activate and regulate postsynaptic responses. Both AMPA and NMDA receptors are fundamental mediators of synaptic plasticity, the ability of synapses to strengthen or weaken, where dysregulation of those receptors leads to neurodegeneration in a variety of disorders, including Alzheimer’s disease.
The main difference between AMPA and NMDA receptors is that sodium and potassium increases in AMPA receptors where calcium increases along with sodium and potassium influx in NMDA receptors. Moreover, AMPA receptors do not have a magnesium ion block while NMDA receptors do have a calcium ion block. AMPA and NMDA are two types of ionotropic, glutamate receptors. They are non-selective, ligand-gated ion channels, which mainly enable the passage of sodium and potassium ions. Furthermore, glutamate is a neurotransmitter which creates excitatory postsynaptic signals in the CNS.
What are AMPA Receptors?
AMPA, also known as α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate, receptors are glutamate receptors which are in charge of maintaining the rapid, synaptic transmission in the central nervous system. AMPA receptors have four subunits, GluA1-4. Moreover, the GluA2 subunit is not permeable to calcium ions because it contains arginine from the TMII region.
Furthermore, AMPA receptors are involved in the transmission of the majority of the rapid, excitatory synaptic signals. The increase of the post-synaptic response depends on the amount of receptors in the post-synaptic surface. The type of agonist which activates the AMPA receptors is α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid. The activation of the AMPA receptors leads to the non-selective transportation of cations, such as sodium and potassium ions, into the cell. This generates an action potential in the postsynaptic membrane. Figure 1 below demonstrates a diagram of AMPA receptors.
What are NMDA Receptors?
NMDA, also known as N-methyl-d-aspartate, receptors are glutamate receptors which are found in the postsynaptic membrane. The NMDA receptors are made up of two varieties of subunits: GluN1 and GluN2. The GluN1 subunit is fundamental for the role of the receptor. This subunit can associate with one of the four types of GluN2 subunits, GluN2A-D.
Furthermore, the main utilization of the NMDA receptors is to maintain the synaptic response. In the resting membrane potential, these receptors are inactive due to the creation of a magnesium block. The agonist of the NMDA receptor is N-methyl-d-aspartic acid. L-glutamate, including glycine, can connect to the receptor to activate it. Upon stimulation, NMDA receptors activate the calcium influx along with the potassium and sodium influx. Figure 2 demonstrates NMDA receptors.
Similarities Between AMPA and NMDA Receptors
- AMPA, NMDA, and kainate receptors are the three main types of glutamate receptors.
- These are ligand-gated ion channels which activate and regulate sodium and potassium ions.
- These are known due to the type of agonist which activates the receptor.
- Moreover, the activation of these receptors produces excitatory postsynaptic responses or ESPSs.
- Furthermore, several protein subunits connect together to form these receptors.
Difference Between AMPA and NMDA Receptors
AMPA receptors are best known as a type of glutamate receptor which activates in excitatory neurotransmission and connects α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid which additionally works as a cation channel. Where the NMDA receptors are best known as a type of glutamate receptor which helps in excitatory neurotransmission and also connects N-methyl-D-aspartate. This is the most fundamental difference between AMPA and NMDA receptors.
AMPA receptors have four subunits, GluA1-4 while NMDA receptors have a GluN1 subunit associated with one of the four GluN2 receptors, GluN2A-D. Activation can also be a difference between AMPA and NMDA receptors. AMPA receptors are only activated by glutamate while NMDA receptors are activated by different agonists. The agonist for AMPA receptors is α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid where the agonist for NMDA receptors is N-methyl-d-aspartic acid.
Ion influx is a fundamental difference between AMPA and NMDA receptors. Activation of AMPA receptors results in the sodium and potassium influx while the activation of NMDA receptors leads to an increase in potassium, sodium, and calcium. Another distinction between AMPA and NMDA receptors is that AMPA receptors do not contain a calcium ion where NMDA receptors contain magnesium receptors. Also, AMPA receptors are responsible for the transmission of the majority of the rapid, excitatory synaptic signals while NMDA receptors are responsible for the modulation of the synaptic response.
AMPA receptors are glutamate receptors which lead to the influx of sodium and potassium ions. NMDA receptors are another type of glutamate receptors which result in the influx of calcium ions with potassium and sodium ions. The main difference between AMPA and NMDA receptors is the type of ion influx associated with their activation and regulation.
Several varieties of ionotropic glutamate receptors have been demonstrated in the following article. Three of these main excitatory neurotransmitter in the central nervous system, or CNS, are ligand-gated ion channels best known as AMPA receptors, NMDA receptors, and kainate receptors. These ionotropic glutamate receptors are best referred to after the agonists which activate and regulate them: AMPA or α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate, NMDA or N-methyl-d-aspartate, and kainic acid. – Dr. Alex Jimenez D.C., C.C.S.T. Insight
Diet and Exercise for Neurological Disease
The purpose of the article above is to demonstrate the difference between AMPA and NMDA receptors for brain health. Neurological diseases are associated with the brain, the spine, and the nerves. The scope of our information is limited to chiropractic, musculoskeletal and nervous health issues as well as functional medicine articles, topics, and discussions. To further discuss the subject matter above, please feel free to ask Dr. Alex Jimenez or contact us at 915-850-0900 .
Curated by Dr. Alex Jimenez
Additional Topic Discussion: Chronic Pain
Sudden pain is a natural response of the nervous system which helps to demonstrate possible injury. By way of instance, pain signals travel from an injured region through the nerves and spinal cord to the brain. Pain is generally less severe as the injury heals, however, chronic pain is different than the average type of pain. With chronic pain, the human body will continue sending pain signals to the brain, regardless if the injury has healed. Chronic pain can last for several weeks to even several years. Chronic pain can tremendously affect a patient’s mobility and it can reduce flexibility, strength, and endurance.
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