title: ORL1 receptor-mediated internalization of N-type calcium channels.
abstract: The inhibition of N-type calcium channels by opioid receptor like receptor 1 (ORL1) is a key mechanism for controlling the transmission of nociceptive signals. We recently reported that signaling complexes consisting of ORL1 receptors and N-type channels mediate a tonic inhibition of calcium entry. Here we show that prolonged ( approximately 30 min) exposure of ORL1 receptors to their agonist nociceptin triggers an internalization of these signaling complexes into vesicular compartments. This effect is dependent on protein kinase C activation, occurs selectively for N-type channels and cannot be observed with mu-opioid or angiotensin receptors. In expression systems and in rat dorsal root ganglion neurons, the nociceptin-mediated internalization of the channels is accompanied by a significant downregulation of calcium entry, which parallels the selective removal of N-type calcium channels from the plasma membrane. This may provide a new means for long-term regulation of calcium entry in the pain pathway.
authors.affiliation: Department of Physiology and Biophysics, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Christophe
authors.initials: C
authors.lastname: Altier
authors.forename: Houman
authors.initials: H
authors.lastname: Khosravani
authors.forename: Rhian M
authors.initials: RM
authors.lastname: Evans
authors.forename: Shahid
authors.initials: S
authors.lastname: Hameed
authors.forename: Jean B
authors.initials: JB
authors.lastname: Peloquin
authors.forename: Brian A
authors.initials: BA
authors.lastname: Vartian
authors.forename: Lina
authors.initials: L
authors.lastname: Chen
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Beedle
authors.forename: Stephen S G
authors.initials: SS
authors.lastname: Ferguson
authors.forename: Alexandre
authors.initials: A
authors.lastname: Mezghrani
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Dubel
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bourinet
authors.forename: John E
authors.initials: JE
authors.lastname: McRory
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Zamponi
mesh_terms: D000814:Aniline Compounds; D000818:Animals; D020864:Calcium Channels, N-Type / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D005456:Fluorescent Dyes; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D010146:Pain / Q000503:physiopathology*; D011957:Receptors, Opioid / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014966:Xanthenes; D000094942:Nociceptin Receptor
chemical_list: D000814:Aniline Compounds; C500963:Cacna1b protein, mouse; D020864:Calcium Channels, N-Type; C409648:Fluo 4; D005456:Fluorescent Dyes; D011957:Receptors, Opioid; D014966:Xanthenes; D000094942:Nociceptin Receptor; C000722287:Oprl1 protein, mouse