AMPA receptor
| AMPA receptor | ||
|---|---|---|
|
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| Structure of the GluR subunit (scheme) | ||
| Secondary to quaternary structure | Homo- / heterotetramer | |
| Identifier | ||
| Gene name (s) | GRIA1 , GRIA2 , GRIA3 , GRIA4 | |
| Transporter classification | ||
| TCDB | 1.A.10.1 | |
| designation | glutamate-gated ion channel neurotransmitter receptors | |
AMPA receptors (AMPAR, English α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor ) form in addition to the NMDA and kainate receptors, a subset of the glutamate receptors and are the most common neurotransmitters - receptors in the central nervous system . They form cation channels that mediate the fast component of the postsynaptic current. Their activation causes changes in conductivity in the postsynaptic membrane for a period of a few milliseconds. The AMPA receptors owe their name to the synthetic agonist AMPA ( α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid ), with which they can be specifically activated.
AMPA receptors are made up of four subunits, each with a mass of about 100 kDa . The sequence similarity between the subunits is about 70%. There are four different AMPA receptor subunits called GluR1 , GluR2 to 4 (GluR-A to -D).
The individual subunits consist of around 900 amino acids . The N-termini of the subunits are extracellular, the C-termini intracellular. The polypeptide chain of a subunit crosses the membrane three times and forms a loop in the membrane from the intracellular side. The loops of the four subunits together form the ion channel (see Fig. 1).
The GluR subunits each come in two forms, the so-called flip and flop forms. They differed in the absence or presence of an alternatively spliced exon . It results in 38 amino acid residues preceding the last transmembrane domain. The flip forms of the GluR subunits show a slower desensitization of the AMPA receptor than the flop forms.
The ion specificity of the AMPA receptors (i.e. their relative conductivity for sodium , potassium or calcium ions) depends on the combination of the subunits of which they are composed. In contrast to GluR2 , GluR1 , GluR3 and GluR4 are generally permeable to calcium ions. As a rule, AMPA receptors containing GluR2 are not permeable to calcium ions. This is because the GluR2 subunit transcript is altered by the enzyme adenosine deaminase . This change leads to an amino acid change from glutamine to arginine in the second transmembrane domain . The significantly longer, positively charged side chain of arginine makes the binding of calcium energetically unfavorable and thus prevents the permeability of calcium in 99.99%.
The GluR2 subunit is also important for the relationship between membrane potential and current through the AMPA receptor. The current through receptors without GluR2 is inward rectifying. This means that a current flows through the ion channel only with negative values of the membrane potential , but not with positive values . In the presence of GluR2, however, the current-voltage relationship of AMPA receptors is linear.
AMPA receptors are important for synaptic plasticity . At many synapses , such as B. in the hippocampus or in the cerebellum , the density of AMPA receptors in the postsynaptic membrane is regulated depending on the activity of the synapse.
One AMPA receptor antagonist is NBQX . A negative allosteric modulator is ethanol .
See also
Individual evidence
- ↑ J. Mosbacher, R. Schoepfer, H. Monyer, N. Burnashev, PH. Seeburg, JP. Ruppersberg: A molecular determinant for submillisecond desensitization in glutamate receptors . In: Science . 266, No. 5187, 1994, pp. 1059-1062. doi : 10.1126 / science.7973663 . PMID 7973663 .