Structure and function of glutamate receptor ion channels

Annu Rev Physiol. 2004:66:161-81. doi: 10.1146/annurev.physiol.66.050802.084104.

Abstract

A vast number of proteins are involved in synaptic function. Many have been cloned and their functional role defined with varying degrees of success, but their number and complexity currently defy any molecular understanding of the physiology of synapses. A beacon of success in this medieval era of synaptic biology is an emerging understanding of the mechanisms underlying the activity of the neurotransmitter receptors for glutamate. Largely as a result of structural studies performed in the past three years we now have a mechanistic explanation for the activation of channel gating by agonists and partial agonists; the process of desensitization, and its block by allosteric modulators, is also mostly explained; and the basis of receptor subtype selectivity is emerging with clarity as more and more structures are solved. In the space of months we have gone from cartoons of postulated mechanisms to hard fact. It is anticipated that this level of understanding will emerge for other synaptic proteins in the coming decade.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Crystallization
  • Humans
  • Molecular Sequence Data
  • Protein Structure, Tertiary / physiology
  • Receptors, AMPA / chemistry
  • Receptors, AMPA / metabolism
  • Receptors, Glutamate / chemistry*
  • Receptors, Glutamate / genetics
  • Receptors, Glutamate / metabolism*
  • Receptors, N-Methyl-D-Aspartate / chemistry
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Structure-Activity Relationship

Substances

  • Receptors, AMPA
  • Receptors, Glutamate
  • Receptors, N-Methyl-D-Aspartate