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

Ebru Aydar, Christopher P. Palmer, Vitaly A. Klyachko, Meyer B. Jackson

Research output: Contribution to journalArticle

322 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)399-410
Number of pages12
JournalNeuron
Volume34
Issue number3
DOIs
StatePublished - Apr 25 2002
Externally publishedYes

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