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Dual modulation of CNS voltage-gated calcium channels by cannabinoids: Focus on CB1 receptor-independent effects
Authors:Natalia Lozovaya   Rogier Min   Vera Tsintsadze  Nail Burnashev  
Affiliation:aInstitut de Neurobiologie de la Méditerranée (INMED) INSERM U901, 13273 Marseille Cedex 09, France;bDepartment of Experimental Neurophysiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands;cDepartment of Physiology, University of Bern, 3012 Bern, Switzerland;dDepartment of Cellular Membranology, Bogomoletz Institute of Physiology, 01204 Kiev, Ukraine
Abstract: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.
Keywords:Endocannabinoids   Voltage-gated calcium channels   Anandamide   CB1R-independent effects
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