Regulation of AMPA receptor gating and pharmacology by TARP auxiliary subunits

Aaron D. Milstein, Roger A. Nicoll

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

Presynaptic glutamate release elicits brief waves of membrane depolarization in neurons by activating AMPA receptors. Depending on its precise size and shape, current through AMPA receptors gates downstream processes like NMDA receptor activation and action potential generation. Over a decade of research on AMPA receptor structure and function has identified binding sites on AMPA receptors for agonists, antagonists and allosteric modulators as well as key residues underlying differences in the gating behavior of various AMPA receptor subtypes. However, the recent discovery that AMPA receptors are accompanied in the synaptic membrane by a family of auxiliary subunits known as transmembrane AMPA receptor regulatory proteins (TARPs) has revealed that the kinetics and pharmacology of neuronal AMPA receptors differ in many respects from those predicted by classical studies of AMPA receptors in heterologous systems. Here, we summarize recent work and discuss remaining questions concerning the structure and function of native TARP-AMPA receptor complexes.

Original languageEnglish (US)
Pages (from-to)333-339
Number of pages7
JournalTrends in Pharmacological Sciences
Volume29
Issue number7
DOIs
StatePublished - Jul 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

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