Cannabinoid receptor agonists modulate calcium channels in rat retinal müller cells
Cannabinoid receptor agonists modulate calcium channels in rat retinal müller cells
复制标题
DOI：
10.1016/j.neuroscience.2015.11.039
复制
发表时间：
2016-01
期刊：
影响因子：
3.3
通讯作者：
W. Yang;Qian Li;Shu-Yue Wang;F. Gao;Wenjing Qian;Fei Li;M. Ji;X. H. Sun-X. H.-Sun-2125992417;Y. Miao;Zhongfeng Wang
中科院分区：
文献类型：
--
作者：
W. Yang;Qian Li;Shu-Yue Wang;F. Gao;Wenjing Qian;Fei Li;M. Ji;X. H. Sun-X. H.-Sun-2125992417;Y. Miao;Zhongfeng Wang
虽然大麻素CB1受体（CB1R）的激活通过调节这些细胞中的离子通道来调节各种视网膜神经元功能，但激活的大麻素受体对视网膜<s:1> ller细胞中Ca2+通道的影响仍在很大程度上未知。在本研究中，我们通过免疫荧光染色发现，t型Ca2+通道CaV3.1、CaV3.2和CaV3.3三个亚基，以及l型Ca2+通道CaV1.2一个亚基在大鼠<s:1> ller细胞中表达。一致地，尼莫地平和米贝弗拉地尔敏感的Na+电流通过L型和t型Ca2+通道可以记录电生理。大麻素受体激动剂WIN55212-2对急性离体大鼠心肌细胞Ca2+通道电流（以t型为主）呈剂量依赖性抑制，ic50值为3.98 μM。WIN55212-2的作用未被AM251/SR141716特异性CB1R拮抗剂阻断。当大麻素受体的内源性配体anandamide （AEA）和2-花生四烯醇甘油（2-AG）被应用时，也观察到类似的电流抑制。此外，尽管CB2受体（CB2Rs）在大鼠<s:1> ller细胞中表达，但WIN55212-2和2-AG对Ca2+通道电流的影响不会被AM630（一种选择性CB2R拮抗剂）阻断。而AM630能部分缓解AEA的作用。这些结果表明，WIN55212-2和2-AG受体独立抑制<s:1> ller细胞中的Ca2+通道电流，而AEA通过CB2Rs部分抑制Ca2+通道电流。受体依赖性和非依赖性机制的存在表明大麻素可能通过多种途径调节<s:1> ller细胞功能。
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 Müller cells is still largely unknown. In the present work we show that three subunits of T-type Ca2+channels, CaV3.1, CaV3.2 and CaV3.3, as well as one subunit of L-type Ca2+channels, CaV1.2, were expressed in rat Müller 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 Müller cells in a dose-dependent manner, with an IC50of 3.98 μM. 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 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 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.