ORL1 receptor-mediated internalization of N-type calcium channels

Nat Neurosci. 2006 Jan;9(1):31-40. doi: 10.1038/nn1605. Epub 2005 Nov 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds
  • Animals
  • Calcium Channels, N-Type / genetics
  • Calcium Channels, N-Type / physiology*
  • Cells, Cultured
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Electrophysiology
  • Fluorescent Dyes
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / metabolism
  • Ganglia, Spinal / physiology
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • Microscopy, Confocal
  • Pain / physiopathology*
  • Receptors, Opioid / agonists
  • Receptors, Opioid / genetics
  • Receptors, Opioid / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Xanthenes

Substances

  • Aniline Compounds
  • Cacna1b protein, mouse
  • Calcium Channels, N-Type
  • Fluo 4
  • Fluorescent Dyes
  • Receptors, Opioid
  • Xanthenes
  • nociceptin receptor