ORL1 receptor–mediated internalization of N-type calcium channels Academic Article uri icon

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  • 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
  • Khosravani, Houman
  • Evans, Rhian M
  • Hameed, Shahid
  • Peloquin, Jean B
  • Vartian, Brian
  • Chen, Lina
  • Beedle, Aaron M
  • Ferguson, Stephen SG
  • Mezghrani, Alexandre
  • Dubel, Stefan J
  • Bourinet, Emmanuel
  • McRory, John E
  • Zamponi, Gerald W

publication date

  • January 2006

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