Signaling complexes of voltage-gated calcium channels and G protein-coupled receptors

J Recept Signal Transduct Res. 2008;28(1-2):71-81. doi: 10.1080/10799890801941947.


Activation of opioid or opioid-receptor-like (ORL1 a.k.a. NOP or orphanin FQ) receptors mediates analgesia through inhibition of N-type calcium channels in dorsal root ganglion (DRG) neurons (1, 2). Unlike the three types of classical mu, delta, and kappa opioid receptors, ORL1 mediates an agonist-independent inhibition of N-type calcium channels. This is mediated via the formation of a physical protein complex between the receptor and the channel, which in turn allows the channel to effectively sense a low level of constitutive receptor activity (3). Further inhibition of N-type channel activity by activation of other G protein-coupled receptors is thus precluded. ORL1 receptors, however, also undergo agonist-induced internalization into lysosomes, and channels thereby become cointernalized in a complex with ORL1. This then results in removal of N-type channels from the plasma membrane and reduced calcium entry (4). Similar signaling complexes between N-type channels and GABA(B) receptors have been reported (5). Moreover, both L-type and P/Q-type channels appear to be able to associate with certain types of G protein-coupled receptors (6, 7). Hence, interactions between receptors and voltage-gated calcium channels may be a widely applicable means to optimize receptor channel coupling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium Channels / chemistry*
  • Calcium Channels / classification
  • Calcium Channels / metabolism*
  • Calcium Channels, L-Type / chemistry
  • Calcium Channels, L-Type / metabolism
  • Calcium Channels, N-Type / chemistry
  • Calcium Channels, N-Type / metabolism
  • Humans
  • Models, Biological
  • Multiprotein Complexes
  • Nociceptin Receptor
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Opioid / chemistry
  • Receptors, Opioid / metabolism
  • Signal Transduction


  • Calcium Channels
  • Calcium Channels, L-Type
  • Calcium Channels, N-Type
  • Multiprotein Complexes
  • Receptors, G-Protein-Coupled
  • Receptors, Opioid
  • Nociceptin Receptor
  • OPRL1 protein, human