Dual modulation of CNS voltage-gated calcium channels by cannabinoids: Focus on CB1 receptor-independent effects.
The neuromodulatory effects of cannabinoids in the central nervous system have mainly been associated with G-protein coupled cannabinoid receptor (CB1R) mediated inhibition of voltage-gated calcium channels (VGCCs). Numerous studies show, however, that cannabinoids can also modulate VGCCs independent of CB1R activation. Nevertheless, despite the fact that endocannabinoids have a nearly equal efficacy for direct and CB1R-mediated effects on VGCC, the role of the direct cannabinoid-VGCC interaction has been largely underestimated. In this review, we summarize recent studies on the modulation of different types of VGCCs by cannabinoids, highlight the evidence for and implications of the CB1R-independent modulation, and put forward the concept, that direct interaction of cannabinoids and VGCCs is as important in regulation of VGCCs function as the CB1R-mediated effects.
Lozovaya
Natalia
N
Institut de Neurobiologie de la Méditerranée INSERM U, Marseille, France.
Min
Rogier
R
Tsintsadze
Vera
V
Burnashev
Nail
N
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology*; D002490:Central Nervous System / Q000502:physiology*; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D020033:Protein Isoforms / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D015398:Signal Transduction
D001095:Arachidonic Acids; D015220:Calcium Channels; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D020033:Protein Isoforms; D043884:Receptor, Cannabinoid, CB1; C078814:anandamide