The sigma receptor as a ligand-regulated auxiliary potassium channel subunit.
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.
Aydar
Ebru
E
Department of Physiology, School of Medicine, University of Wisconsin-Madison, 1300 University Avenue, Madison, WI 53706, USA.
Palmer
Christopher P
CP
Klyachko
Vitaly A
VA
Jackson
Meyer B
MB
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D051665:Kv1.4 Potassium Channel; D051666:Kv1.5 Potassium Channel; D008024:Ligands; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010904:Pituitary Gland, Posterior / Q000737:chemistry / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D017433:Protein Structure, Secondary; D021122:Protein Subunits; D051381:Rats; D017480:Receptors, sigma / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014982:Xenopus laevis
D014150:Antipsychotic Agents; C496979:Kcna4 protein, rat; C496983:Kcna5 protein, rat; D051665:Kv1.4 Potassium Channel; D051666:Kv1.5 Potassium Channel; D008024:Ligands; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D017480:Receptors, sigma; D011993:Recombinant Fusion Proteins; C012134:SK&F 10047; D010620:Phenazocine