What is the difference between synaptic and Extrasynaptic?
What is the difference between synaptic and Extrasynaptic?
Synaptic NMDARs are generally transiently and intensely activated by the trans-synaptic release of glutamate, while extrasynaptic NMDARs are typically activated chronically, by elevated levels of ambient glutamate.
What are Extrasynaptic sites?
Extrasynaptic NMDA receptors are glutamate-gated neurotransmitter receptors that are localized to non-synaptic sites on the neuronal cell surface.
How does the NMDA receptor detect an action potential in the postsynaptic cell?
Glutamate binds to the NMDA receptor, opening it to allow Ca++ ions to flow into the postsynaptic cell. Because these AMPA receptors provide the primary excitatory input drive on the neuron, changing them changes the net excitatory effect of a presynaptic action potential on the postsynaptic neuron.
What does the term Extrasynaptic mean?
Extrasynaptic transmission is a unifying term for a wide variety of cellular processes, in which outside of synaptic terminals transmitter substances activate extrasynaptic receptors.
What is the biological purpose of Excitotoxicity?
Excitotoxicity is a phenomenon that describes the toxic actions of excitatory neurotransmitters, primarily glutamate, where the exacerbated or prolonged activation of glutamate receptors starts a cascade of neurotoxicity that ultimately leads to the loss of neuronal function and cell death.
Where are AMPA and NMDA receptors located?
NMDA receptors are neurotransmitter receptors that are located in the post-synaptic membrane of a neuron. They are proteins embedded in the membrane of nerve cells that receive signals across the synapse from a previous nerve cell.
What is AMPA receptor?
The AMPA receptor (AMPA-R) is a subtype of the ionotropic glutamate receptor coupled to ion channels that modulate cell excitability by gating the flow of calcium and sodium ions into the cell (Doble, 1995). From: Drug Discovery Approaches for the Treatment of Neurodegenerative Disorders, 2017.
How do AMPA and NMDA receptors work together?
The AMPA receptor is paired with an ion channel so that when glutamate binds to this receptor, this channel lets sodium ions enter the post-synaptic neuron. The NMDA receptor is also paired with an ion channel, but this channel admits calcium ions into the post-synaptic cell.
Where does excitotoxicity occur?
Excitotoxicity occurs when neurons are exposed to high levels of glutamate that causes a persistent activation of the N-methyl-d-aspartate acid (NMDA) and α-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) receptors and voltage-gated calcium channels resulting in a lethal influx of extracellular calcium.
What is the difference between NMDA and AMPA receptors?
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.
What is the difference between synaptic and extrasynaptic NMDAR?
According to this new model, synaptic NMDARs are neuroprotective, whereas extrasynaptic NMDARs preferentially initiate cell death pathways. Thus, the fate of neurons is not determined solely by the degree of overall NMDAR activity but by the extent to which synaptic and extrasynaptic NMDARs are activated.
What happens when NMDAR receptors are activated?
Recent studies show that NMDAR-induced responses depend on the receptor location: stimulation of synaptic NMDARs, acting primarily through nuclear Ca2+signaling, leads to the build-up of a neuroprotective ‘shield’, whereas stimulation of extrasynaptic NMDARs promotes cell death.
Do extrasynaptic NMDARs have a role in pathological scenarios?
This Review will focus on the emerging role of extrasynaptic NMDARs in pathological scenarios and contrast it against the demonstrated survival-promoting effects of synaptic NMDAR activity.
What is the role of extrasynaptic NMDAR signalling in Huntington’s disease?
A shift in the balance from synaptic towards extrasynaptic NMDAR signalling may be an important factor in the aetiology of neurodegenerative diseases. In Huntington’s disease, mutant huntingtin causes a specific increase in extrasynaptic NMDAR currents.
