CANNABINOID RECEPTOR AGONISTS MODULATE CALCIUM CHANNELS IN RAT RETINAL MULLER CELLS

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 Ca2+ channels in retinal Muller cells is still largely unknown. In the present work we show that three subunits of T-type Ca2+ channels, Ca(V)3.1, Ca(V)3.2 and Ca(V)3.3, as well as one subunit of L-type Ca2+ channels, Ca(V)1.2, were expressed in rat Muller cells by immunofluorescent staining. Consistently, nimodipine-and mibefradil-sensitive Na+ currents through L-and T-type Ca2+ channels could be recorded electrophysiologically. The cannabinoid receptor agonist WIN55212-2 significantly suppressed Ca2+ channel currents, mainly the T-type one, in acutely isolated rat Muller cells in a dose-dependent manner, with an IC50 of 3.98 mu M. 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 Muller cells, the effects of WIN55212-2 and 2-AG on Ca2+ 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 Ca2+ channel currents in Muller cells, while AEA suppressed the currents partially through CB2Rs. The existence of receptor-dependent and -independent mechanisms suggests that cannabinoids may modulate Muller cell functions through multiple pathways. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.