Signaling complexes of voltage-gated calcium channels and G protein-coupled receptors.
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.
Altier
Christophe
C
Hotchkiss Brain Institute, Department of Physiology and Biophysics, University of Calgary, Canada.
Zamponi
Gerald W
GW
D000818:Animals; D015220:Calcium Channels / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D046912:Multiprotein Complexes; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*; D011957:Receptors, Opioid / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D000094942:Nociceptin Receptor
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D046912:Multiprotein Complexes; D043562:Receptors, G-Protein-Coupled; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; C000722283:OPRL1 protein, human