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Cannabinoid receptor agonists modulate calcium channels in rat retinal Müller cells.
Neuroscience. 2016 Jan 28; 313:213-24.N

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.

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Authors+Show Affiliations

Yang W
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.
Li Q
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.
Wang SY
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.
Gao F
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.
Qian WJ
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.
Li F
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.
Ji M
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.
Sun XH
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.
Miao Y
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.
Wang Z
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.

MeSH

AnimalsArachidonic AcidsBenzoxazinesCalciumCalcium ChannelsCannabinoid Receptor AgonistsCannabinoid Receptor AntagonistsCells, CulturedDose-Response Relationship, DrugEndocannabinoidsEpendymoglial CellsGlyceridesIndolesMaleMembrane PotentialsMorpholinesNaphthalenesPiperidinesPolyunsaturated AlkamidesPyrazolesRats, Sprague-DawleyReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2Rimonabant

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26621126

Citation

Yang, W, et al. "Cannabinoid Receptor Agonists Modulate Calcium Channels in Rat Retinal Müller Cells." Neuroscience, vol. 313, 2016, pp. 213-24.
Yang W, Li Q, Wang SY, et al. Cannabinoid receptor agonists modulate calcium channels in rat retinal Müller cells. Neuroscience. 2016;313:213-24.
Yang, W., Li, Q., Wang, S. Y., Gao, F., Qian, W. J., Li, F., Ji, M., Sun, X. H., Miao, Y., & Wang, Z. (2016). Cannabinoid receptor agonists modulate calcium channels in rat retinal Müller cells. Neuroscience, 313, 213-24. https://doi.org/10.1016/j.neuroscience.2015.11.039
Yang W, et al. Cannabinoid Receptor Agonists Modulate Calcium Channels in Rat Retinal Müller Cells. Neuroscience. 2016 Jan 28;313:213-24. PubMed PMID: 26621126.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid receptor agonists modulate calcium channels in rat retinal Müller cells. AU - Yang,W, AU - Li,Q, AU - Wang,S-Y, AU - Gao,F, AU - Qian,W-J, AU - Li,F, AU - Ji,M, AU - Sun,X-H, AU - Miao,Y, AU - Wang,Z, Y1 - 2015/11/24/ PY - 2015/08/19/received PY - 2015/11/10/revised PY - 2015/11/17/accepted PY - 2015/12/2/entrez PY - 2015/12/2/pubmed PY - 2016/10/1/medline KW - 2-arachidonoyl glycerol KW - CB1/CB2 receptors KW - Müller cells KW - WIN55212-2 KW - anandamide KW - calcium channel SP - 213 EP - 24 JF - Neuroscience JO - Neuroscience VL - 313 N2 - 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. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/26621126/Cannabinoid_receptor_agonists_modulate_calcium_channels_in_rat_retinal_Müller_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(15)01038-6 DB - PRIME DP - Unbound Medicine ER -