Recent advances in the study of AMPA receptors

Takeshi Suzuki, Keisuke Tsuzuki, Kimihiko Kameyama, Shin Kwak

Research output: Contribution to journalReview article

16 Citations (Scopus)

Abstract

As glutamate is a dominant excitatory neurotransmitter in the central nervous system, glutamate receptors, and especially AMPA receptors, are located ubiquitously in all brain areas. In this paper, we reviewed recent advances of studies on AMPA receptor functions. AMPA receptors are cation-conducting complexes composed of various combinations of four subunits (GluR1 to GluR4). The glutamine residue located in the pore-forming segment of GluR2 subunit (Q/R site) is changed to arginine by RNA editing at the pre mRNA stage in normal adult mammalian animal. The edited GluR2 subunit is a major determination of Ca2+ permeability of the AMPA receptor; only edited GluR2-lacking receptor shows high-Ca2+ permeability, The assembly of glutamate AMPA receptor subunit is not completely according to the stochastic theory. The heteromeric subunits assembly is more rapid than the homomeric assembly is, The transfer of AMPA receptor subunit to the plasma membrane is conducted in multiple ways. Many molecules that interact with the intracellular domain of AMPA receptor subunits are reported as the modulators of AMPA receptor subunit transfer. In the motoneuron of sporadic amyotrophic lateral sclerosis (ALS) patients, the efficiency of RNA editing at the GluR2 Q/R site is significantly decreased. Relative low level of edited GluR2 subunit expression is likely responsible for motoneuronal death in ALS. Recently, AMPA receptors in glial cells have been studied. Bergmann glial cells in cerebellum express Ca 2+-permeable AMPA receptors. Conversion of these AMPA receptors to Ca2+-impermeable type receptors induces morphological and functional changes. Glioblastoma cells also express Ca2+-permeable AMPA receptors, and their conversion to Ca2+ impermeable receptors inhibits cell locomotion and induces apoptosis.

Original languageEnglish
Pages (from-to)515-526
Number of pages12
JournalFolia Pharmacologica Japonica
Volume122
Issue number6
DOIs
Publication statusPublished - 2003 Dec 1

Keywords

  • AMPA receptor
  • Amyotrophic lateral sclerosis (ALS)
  • Calcium
  • Glutamate
  • RNA editing

ASJC Scopus subject areas

  • Pharmacology

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