The sigma receptor as a ligand-regulated auxiliary potassium channel subunit

Neuron. 2002 Apr 25;34(3):399-410. doi: 10.1016/s0896-6273(02)00677-3.


The sigma receptor is a novel protein that mediates the modulation of ion channels by psychotropic drugs through a unique transduction mechanism depending neither on G proteins nor protein phosphorylation. The present study investigated sigma receptor signal transduction by reconstituting responses in Xenopus oocytes. Sigma receptors modulated voltage-gated K+ channels (Kv1.4 or Kv1.5) in different ways in the presence and absence of ligands. Association between Kv1.4 channels and sigma receptors was demonstrated by coimmunoprecipitation. These results indicate a novel mechanism of signal transduction dependent on protein-protein interactions. Domain accessibility experiments suggested a structure for the sigma receptor with two cytoplasmic termini and two membrane-spanning segments. The ligand-independent effects on channels suggest that sigma receptors serve as auxiliary subunits to voltage-gated K+ channels with distinct functional interactions, depending on the presence or absence of ligand.

Publication types

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

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology
  • Kv1.4 Potassium Channel
  • Kv1.5 Potassium Channel
  • Ligands
  • Oocytes / drug effects
  • Oocytes / physiology
  • Patch-Clamp Techniques
  • Phenazocine / analogs & derivatives*
  • Phenazocine / pharmacology
  • Pituitary Gland, Posterior / chemistry
  • Pituitary Gland, Posterior / metabolism
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Potassium Channels, Voltage-Gated*
  • Protein Structure, Secondary
  • Protein Subunits
  • Rats
  • Receptors, sigma / chemistry
  • Receptors, sigma / genetics
  • Receptors, sigma / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / physiology*
  • Xenopus laevis


  • Antipsychotic Agents
  • Kcna4 protein, rat
  • Kcna5 protein, rat
  • Kv1.4 Potassium Channel
  • Kv1.5 Potassium Channel
  • Ligands
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Protein Subunits
  • Receptors, sigma
  • Recombinant Fusion Proteins
  • SK&F 10047
  • Phenazocine