Cannabinoid CB1 and CB2 receptors differentially modulate L- and T-type Ca2+ channels in rat retinal ganglion cells. (15th September 2017)

• Record Type: Journal Article
• Authors: Qian, Wen-Jing; Yin, Ning; Gao, Feng; Miao, Yanying; Li, Qian; Li, Fang; Sun, Xing-Huai; Yang, Xiong-Li; Wang, Zhongfeng
• Is Part Of: Neuropharmacology. Volume 124(2017)
• Page Start: 143
• Page End: 156
• Publication Date: 2017-09-15
• Subjects: CB1Rs -- CB2Rs -- L-type Ca2+ channels -- T-type Ca2+ channels -- Retinal ganglion cells; 2-arachidonoylglycerol 2-AG -- anandamide AEA -- bisindolylmaleimide IV Bis IV -- central nervous system CNS -- cannabinoid CB1 receptor CB1R -- cannabinoid CB2 receptor CB2R -- cannabinoid receptors CBRs -- calcium/calmodulin-dependent protein kinase II CaMKII -- endocannabinoids eCBs -- cholera toxin B subunit CTB -- dimethyl sulfoxide DMSO -- extracellular signal-regulated kinase ERK -- ganglion cell layer GCL -- inner nuclear layer INL -- inner plexiform layer IPL -- mitogen-activated protein kinase MAPK -- outer nuclear layer ONL -- outer plexiform layer OPL -- protein kinase A PKA -- phospholipase C PLC -- rhodamine-B-isothiocyanate RITC -- retinal ganglion cells RGCs -- tetrodotoxin TTX; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2017.04.027
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Endocannabinoid signaling system is involved in regulating multiple neuronal functions in the central nervous system by activating G-protein coupled cannabinoid CB1 and CB2 receptors (CB1Rs and CB2Rs). Growing evidence has shown that CB1Rs and CB2Rs are extensively expressed in retinal ganglion cells (RGCs). Here, modulation of L- and T-types Ca 2+ channels by activating CB1Rs and CB2Rs in RGCs was investigated. Triple immunofluorescent staining showed that L-type subunit CaV 1.2 was co-localized with T-type subunits (CaV 3.1, CaV 3.2 and CaV 3.3) in rat RGCs. In acutely isolated rat RGCs, the CB1R agonist WIN55212-2 suppressed both peak and steady-state Ca 2+ currents in a dose-dependent manner, with IC50 being 9.6 μM and 8.4 μM, respectively. It was further shown that activation of CB1Rs by WIN55212-2 or ACEA, another CB1R agonist, significantly suppressed both L- and T-type Ca 2+ currents, and shifted inactivation curve of T-type one toward hyperpolarization direction. While the effect on L-type Ca 2+ channels was mediated by intracellular cAMP/protein kinase A (PKA), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and calcium/calmodulin-dependent protein kinase II (CaMKII) signaling pathways, only CaMKII signaling pathway was involved in the effect on T-type Ca 2+ channels. Furthermore, CB65 and HU308, two specific CB2R agonists, significantly suppressed T-type Ca 2+ channels, which was mediated by intracellular cAMP/PKA and CaMKII signaling pathways, but had no effect on L-type channels. These results imply that endogenous cannabinoids may modulate the excitability and the output of RGCs by differentially suppressing the activity of L- and T-type Ca 2+ channels through activation of CB1Rs and CB2Rs. This article is part of the Special Issue entitled "A New Dawn in Cannabinoid Neurobiology". Highlights: CaV 1.2 is co-localized with CaV 3.1, CaV 3.2 and CaV 3.3 in rat RGCs. Activation of CB1Rs suppresses both L- and T-types Ca 2+ currents in RGCs. Activation of CB2Rs suppresses T-type Ca 2+ currents in RGCs, but not L-type one. Different signaling pathways mediate the CB1R and CB2R effects on Ca 2+ currents.