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大麻素对人和小鼠视网膜神经节细胞GABA电流的调控差异

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Keywords: 人视网膜,大麻素受体,神经节细胞,全细胞膜片钳技术

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Abstract:

目的比较人和小鼠视网膜内源性大麻素类受体1(cannabinoidreceptor,CB1)的表达差异,观察大麻素受体激动剂WIN55212-2对不同种属视网膜神经节细胞GABA电流的调控作用。方法采用冰冻切片免疫荧光染色,观察CB1受体在视网膜中的表达。制备视网膜薄片,行全细胞膜片钳记录。在神经节细胞上给予100μmol/LGABA快速加药诱导出电流IGABA,而后观察孵育大麻素受体激动剂WIN55212-2时GABA诱导的I?GABA及同时孵育WIN55212-2和大麻素受体拮抗剂SR141716A的电流IGABA。结果人和小鼠视网膜CB1受体的分布有所不同,人的内核层、外核层、神经节细胞层有显著的CB1表达,但小鼠CB1受体主要表达在内网状层、外网状层上;膜片钳结果显示不管是在人还是在小鼠的视网膜上,孵育WIN55212-2后的GABA诱导电流幅度均有显著减小。不同的是,在人视网膜神经节细胞上,WIN55212-2明显减慢了GABA电流的反应速度,表现在电流达峰时间明显延长,恢复时间缩短(P<0.05)。WIN55212-2对小鼠视网膜神经节细胞GABA的反应速度无明显差别(P>0.05)。结论CB1受体在人和小鼠视网膜中有差异性分布,对神经节细胞的GABA电流影响也不同。孵育WIN55212-2可抑制人和小鼠神经节细胞GABA电流幅度,但仅对人的神经节细胞的GABA电流的动力学速度有影响。

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