Assessment | Biopsychology | Comparative | Cognitive | Developmental | Language | Individual differences | Personality | Philosophy | Social |
Methods | Statistics | Clinical | Educational | Industrial | Professional items | World psychology |

Biological: Behavioural genetics · Evolutionary psychology · Neuroanatomy · Neurochemistry · Neuroendocrinology · Neuroscience · Psychoneuroimmunology · Physiological Psychology · Psychopharmacology (Index, Outline)

The α-amino-3-hydroxy-5-methylisoxazole-4- propionic acid AMPA receptor (AMPAR, also known as quisqualate receptor) is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system (CNS). Its name is derived from its ability to be activated by the artificial glutamate analog, AMPA. AMPARs are found in many parts of the brain and are the most commonly found receptor in the nervous system.

Structure and function Edit

AMPARs are composed of four types of subunits, designated as GluR1, GluR2, GluR3, and GluR4 (alternatively called GluRA-D), which combine to form tetramers [1], [2], [3]. Most AMPARs are either homo-tetramers of GluR1 or GluR4, or symmetric 'dimer of dimers' of GluR2/3 and either GluR1 or GluR4.

The conformation of the subunit protein in the plasma membrane caused controversy for some time. While the amino acid sequence of the subunit indicated that there were four transmembrane domains ( parts of the protein that pass through the plasma membrane), proteins interacting with the subunit indicated that the N-terminus was extracellular while the C-terminus was intracellular. If each of the four transmembrane domains went all the way through the plasma membrane, then the two termini would have to be on the same side of the membrane. Eventually, it was discovered that the second transmembrane domain isn't in fact trans at all, but kinks back on itself within the membrane and returns to the intracellular side [4]. When the four subunits of the tetramer come together, this second membranous domain forms the ion-permeable pore of the receptor.

Each AMPAR has four sites to which a molecule of the agonist (such as glutamate) can bind, one in each subunit. The channel can open when two or more sites are occupied [5]. AMPARs open and close quickly, and are thus responsible for most of the fast excitatory synaptic transmission in the central nervous system [6].

The AMPAR's permeability to calcium and other cations, such as sodium and potassium, is governed by the GluR2 subunit. If an AMPAR lacks a GluR2 subunit, then it will be permeable to sodium, potassium and calcium. The presence of a GluR2 subunit will almost certainly render the channel impermeable to calcium [2]. This is determined by post-transcriptional modification - RNA editing - of the Q/R editing site of the GluR2 mRNA. Here, editing alters the uncharged amino acid glutamine (Q), to the positively-charged arginine (R) in the receptor's ion channel. The positively-charged amino acid at the critical point makes it energetically unfavourable for calcium to enter the cell through the pore. Almost all of the GluR2 subunits in CNS are edited to the GluR2(R) form. This means that the principal ions gated by AMPARs are sodium and potassium. The prevention of calcium entry into the cell on activation of GluR2-containing AMPARs is proposed to guard against excitotoxicity [7]

The subunit composition of the AMPAR is also important for the way this receptor is modulated. If an AMPAR lacks GluR2 subunits, then it is susceptible to being blocked in a voltage-dependent manner by a class of molecules called polyamines. Thus when the neuron is at a depolarized membrane potential, polyamines will block the AMPAR channel more strongly, preventing the flux of ions through the channel pore. GluR2-lacking AMPARs are thus said to have an inwardly rectifying I/V curve, which means that they pass less outward current than inward current.

Alongside RNA editing, alternative splicing allows a range of functional AMPA receptor subunits beyond what is encoded in the genome. In other words, although one gene (GRIA1-4) is encoded for each subunit (GluR1-4), splicing after transcription from DNA allows some exons to be translated interchangeably, leading to several functionally different subunits from each gene.

The flip/flop sequence is one such interchangeable exon. A 38-amino acid sequence found prior to (ie towards the N-terminus of) the 4th membranous domain in all four AMPAR subunits, it determines the speed of desensitisation [8] of the receptor and also the speed at which the receptor is resensitised [9].


References Edit

  1. Glutamate receptors: Structures and functions. University of Bristol Centre for Synaptic Plasticity. Free text
  2. The role of glutamate in central nervous system health and disease — A review. Vet J. 2005 Dec 20; [Epub ahead of print] Abstract
  3. Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. Science. 1999 Jun 11; 284(5421): 1811-6 Abstract
  4. N-glycosylation site tagging suggests a three transmembrane domain topology for the glutamate receptor GluR1. Hollmann et al., Neuron 13(6):1331 Abstract
  5. Regulation of AMPA receptors during synaptic plasticity. Trends Neurosci. 2002 Nov; 25(11): 578-88. Abstract
  6. The glutamate receptor ion channels. Pharmacol Rev. 1999 Mar;51(1):7-61. Free text
  7. Abundance of GluR1 mRNA and reduced Q/R editing of GluR2 mRNA in individual NADPH-diaphorase neurons Kim et al., Mol. Cell. Neurosci. 2001 Jun;17(6):1025-33 Abstract
  8. A molecular determinant for submillisecond desensitization in glutamate receptors. Mosbacher et al., Science 1994. Nov 11;266(5187):1059-62 Abstract
  9. Flip and flop: a cell-specific functional switch in glutamate-operated channels of the CNS. Sommer et al., Science 1990. Sep 28;249(4976):1580-5 Abstract

External link Edit

This page uses Creative Commons Licensed content from Wikipedia (view authors).

Ad blocker interference detected!

Wikia is a free-to-use site that makes money from advertising. We have a modified experience for viewers using ad blockers

Wikia is not accessible if you’ve made further modifications. Remove the custom ad blocker rule(s) and the page will load as expected.