ORL1 receptor-mediated internalization of N-type calcium channels.
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.
Altier
Christophe
C
Department of Physiology and Biophysics, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Khosravani
Houman
H
Evans
Rhian M
RM
Hameed
Shahid
S
Peloquin
Jean B
JB
Vartian
Brian A
BA
Chen
Lina
L
Beedle
Aaron M
AM
Ferguson
Stephen S G
SS
Mezghrani
Alexandre
A
Dubel
Stefan J
SJ
Bourinet
Emmanuel
E
McRory
John E
JE
Zamponi
Gerald W
GW
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
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