Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (GluR1-4 or GRIA1-4) are the primary mediators of fast excitatory synaptic transmission in the mammalian central nervous system. [1] AMPA receptors have become recognized as fundamental to learning, memory, and information processing in the brain. The four subunits assemble in various combinations to form functional ion channels with distinct properties. [2]
AMPA receptors are essential for synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), the cellular correlates of learning and memory. Dysfunction of AMPA receptor trafficking and function has been strongly implicated in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). [3][4]
| AMPA Receptor | |
|---|---|
| Protein Name | AMPA Receptor |
| Gene Symbols | GRIA1, GRIA2, GRIA3, GRIA4 |
| UniProt IDs | P42262, P42263, P42264, P42265 |
| Subunit Composition | Tetrameric |
| Subcellular Localization | Postsynaptic density, dendritic spines |
| Associated Diseases | AD, PD, ALS, Epilepsy, Schizophrenia |
AMPA receptor subunits have four domains:
| Subunit | Gene | Calcium Permeability | Key Properties |
|---|---|---|---|
| GluR1 | GRIA1 | High | LTP-critical |
| GluR2 | GRIA2 | Low | Calcium-impermeable, edited |
| GluR3 | GRIA3 | High | Autism link |
| GluR4 | GRIA4 | High | Developmental |
AMPA receptors mediate the majority of fast glutamatergic neurotransmission. When glutamate is released, it binds to AMPA receptors, triggering Na⁺ influx and rapid depolarization.
Hollmann M, Heinemann S. Cloned glutamate receptors. Annual Review of Neuroscience. 1992. ↩︎
Dingledine R, Borges K, Bowie D, Traynelis SF. The glutamate receptor ion channels. Pharmacological Reviews. 1999. ↩︎
Whitcomb DJ, Hogg S, Regan P, et al. AMPA receptor dysfunction in Alzheimer's disease. Journal of Neuroscience. 2020. ↩︎ ↩︎
Zhou W, Li J, Wang J, et al. AMPA receptor trafficking in Parkinson's disease. Neurobiology of Disease. 2019. ↩︎