title: Cannabinoid receptor agonists modulate calcium channels in rat retinal Müller cells.
abstract: While activation of cannabinoid CB1 receptor (CB1R) regulates a variety of retinal neuronal functions by modulating ion channels in these cells, effect of activated cannabinoid receptors on Ca(2+) channels in retinal Müller cells is still largely unknown. In the present work we show that three subunits of T-type Ca(2+) channels, CaV3.1, CaV3.2 and CaV3.3, as well as one subunit of L-type Ca(2+) channels, CaV1.2, were expressed in rat Müller cells by immunofluorescent staining. Consistently, nimodipine- and mibefradil-sensitive Na(+) currents through L- and T-type Ca(2+) channels could be recorded electrophysiologically. The cannabinoid receptor agonist WIN55212-2 significantly suppressed Ca(2+) channel currents, mainly the T-type one, in acutely isolated rat Müller cells in a dose-dependent manner, with an IC50 of 3.98μM. The WIN55212-2 effect was not blocked by AM251/SR141716, specific CB1R antagonists. Similar suppression of the currents was observed when anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), endogenous ligands of cannabinoid receptors, were applied. Moreover, even though CB2 receptors (CB2Rs) were expressed in rat Müller cells, the effects of WIN55212-2 and 2-AG on Ca(2+) channel currents were not blocked by AM630, a selective CB2R antagonist. However, the effect of AEA could be partially rescued by AM630. These results suggest that WIN55212-2 and 2-AG receptor-independently suppressed the Ca(2+) channel currents in Müller cells, while AEA suppressed the currents partially through CB2Rs. The existence of receptor-dependent and -independent mechanisms suggests that cannabinoids may modulate Müller cell functions through multiple pathways.
authors.affiliation: Institutes of Brain Science, Fudan University, Shanghai 200032, China; Institute of Neurobiology, Fudan University, Shanghai 200032, China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China; Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.affiliation: Institutes of Brain Science, Fudan University, Shanghai 200032, China; Institute of Neurobiology, Fudan University, Shanghai 200032, China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China; Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institutes of Brain Science, Fudan University, Shanghai 200032, China; Institute of Neurobiology, Fudan University, Shanghai 200032, China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China; Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Institutes of Brain Science, Fudan University, Shanghai 200032, China; Eye & ENT Hospital, Fudan University, Shanghai 200031, China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai 200031, China; Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: F
authors.initials: F
authors.lastname: Gao
authors.affiliation: Institutes of Brain Science, Fudan University, Shanghai 200032, China; Institute of Neurobiology, Fudan University, Shanghai 200032, China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China; Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: W-J
authors.initials: WJ
authors.lastname: Qian
authors.affiliation: Institutes of Brain Science, Fudan University, Shanghai 200032, China; Institute of Neurobiology, Fudan University, Shanghai 200032, China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China; Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: F
authors.initials: F
authors.lastname: Li
authors.affiliation: Institutes of Brain Science, Fudan University, Shanghai 200032, China; Eye & ENT Hospital, Fudan University, Shanghai 200031, China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai 200031, China; Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: M
authors.initials: M
authors.lastname: Ji
authors.affiliation: Institutes of Brain Science, Fudan University, Shanghai 200032, China; Eye & ENT Hospital, Fudan University, Shanghai 200031, China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai 200031, China; Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: X-H
authors.initials: XH
authors.lastname: Sun
authors.affiliation: Institutes of Brain Science, Fudan University, Shanghai 200032, China; Institute of Neurobiology, Fudan University, Shanghai 200032, China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China; Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.. Electronic address: yymiao@fudan.edu.cn.
authors.forename: Y
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Institutes of Brain Science, Fudan University, Shanghai 200032, China; Eye & ENT Hospital, Fudan University, Shanghai 200031, China; Institute of Neurobiology, Fudan University, Shanghai 200032, China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai 200031, China; Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.. Electronic address: zfwang@fudan.edu.cn.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D048588:Benzoxazines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids / Q000494:pharmacology; D063928:Ependymoglial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005989:Glycerides / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000378:metabolism; D000077285:Rimonabant
chemical_list: D001095:Arachidonic Acids; D048588:Benzoxazines; D015220:Calcium Channels; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; C543264:Cnr1 protein, rat; C469526:Cnr2 protein, rat; D063388:Endocannabinoids; D005989:Glycerides; D007211:Indoles; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C103505:AM 251; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C094503:glyceryl 2-arachidonate; D000077285:Rimonabant; D002118:Calcium; C094023:iodopravadoline; C078814:anandamide
keywords: 2-arachidonoyl glycerol; CB1/CB2 receptors; Müller cells; WIN55212-2; anandamide; calcium channel