• Neuroscience · Jan 2016

    Cannabinoid Receptor Agonists Modulate Calcium Channels in Rat Retinal Müller Cells.

    • W Yang, Q Li, S-Y Wang, F Gao, W-J Qian, F Li, M Ji, X-H Sun, Y Miao, and Z Wang.
    • 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.
    • Neuroscience. 2016 Jan 28; 313: 213-24.

    AbstractWhile 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. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

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