Illuminating the structure and function of Cys-loop receptors

Clin Exp Pharmacol Physiol. 2008 Oct;35(10):1137-42. doi: 10.1111/j.1440-1681.2008.04954.x. Epub 2008 May 25.

Abstract

Cys-loop receptors are an important class of ligand-gated ion channels. They mediate fast synaptic neurotransmission, are implicated in various 'channelopathies' and are important pharmacological targets. Recent progress in X-ray crystallography and electron microscopy has provided a considerable insight into the structure of Cys-loop receptors. However, data from these experiments only provide 'snapshots' of the proteins under investigation. They cannot provide information about the various conformations the protein adopts during transition from the closed to the open and desensitized states. Voltage-clamp fluorometry helps overcome this problem by simultaneously monitoring movements at the channel gate (through changes in current) and conformational rearrangements in a domain of interest (through changes in fluorescence) in real time. Thus, the technique can provide information on both transitional and steady state conformations and serves as a real time correlate of the channel structure and its function. Voltage-clamp fluorometry experiments on Cys-loop receptors have yielded a large body of data concerning the mechanisms by which agonists, antagonists and modulators act on these receptors. They have shed new light on the conformational mobility of both the ligand-binding and the transmembrane domain of Cys-loop receptors.

Publication types

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

MeSH terms

  • Animals
  • Cysteine / chemistry*
  • Cysteine / metabolism
  • Cysteine / physiology*
  • Fluorometry / methods
  • Fluorometry / trends
  • Humans
  • Ion Channel Gating / physiology*
  • Ion Channels / chemistry*
  • Ion Channels / metabolism
  • Ion Channels / physiology*
  • Membrane Proteins / chemistry
  • Membrane Proteins / physiology
  • Patch-Clamp Techniques / methods*
  • Patch-Clamp Techniques / trends

Substances

  • Ion Channels
  • Membrane Proteins
  • Cysteine