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大麻素CB1受体对大鼠视网膜神经节细胞诱发动作电位的作用

蒋淑霞, 李倩, 王霄汉, 李芳, 王中峰^*

复旦大学脑科学研究院，神经生物学研究所，医学神经生物学国家重点实验室，上海 200032

摘要

激活大麻素CB1受体(CB1Rs)通过调控多种离子通道，从而调节脊椎动物视网膜的功能。本文旨在利用膜片钳全细胞记录技术，在大鼠视网膜薄片上研究CB1Rs对神经节细胞兴奋性的作用。结果显示，在电流钳制状态下，灌流CB1R激动剂WIN55212-2 (WIN, 5 μmol/L)对神经节细胞的自发动作电位发放频率和静息膜电位均没有显著影响。在灌流液中加入CNQX，D-APV，bicuculline和strychnine以阻断神经节细胞的兴奋性和抑制性输入，灌流5 μmol/L WIN对正向电流注入(+10 pA到+100 pA)诱发的动作电位的频率也没有显著影响。位相分析结果显示，触发动作电位的阈值电位和触发第一个动作电位的延迟时间在加入WIN前后也没有显著改变；然而，WIN显著降低动作电位的上升和下降相速率(±dV/dtmax)，而且该作用可被CB1R拮抗剂SR141716所阻断。此外，在阻断突触输入的情况下，WIN对神经节细胞的膜电位也没有显著影响。以上结果提示，激活大麻素CB1Rs通过调控诱发动作电位，从而调节大鼠视网膜神经节细胞的兴奋性。

关键词： 动作电位; 大麻素CB1受体; 膜片钳; 神经节细胞; 自发动作电位发放; WIN55212-2

分类号：Q424;Q436

Activation of cannabinoid CB1 receptors modulates evoked action potentials in rat retinal ganglion cells

JIANG Shu-Xia, LI Qian, WANG Xiao-Han, LI Fang, WANG Zhong-Feng^*

Institutes of Brain Science, Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China

Abstract

Activation of cannabinoid CB1 receptors (CB1Rs) regulates a variety of physiological functions in the vertebrate retina through modulating various types of ion channels. The aim of the present study was to investigate the effects of this receptor on cell excitability of rat retinal ganglion cells (RGCs) in retinal slices using whole-cell patch-clamp techniques. The results showed that under current-clamped condition perfusing WIN55212-2 (WIN, 5 μmol/L), a CB1R agonist, did not significantly change the spontaneous firing frequency and resting membrane potential of RGCs. In the presence of cocktail synaptic blockers, including excitatory postsynaptic receptor blockers CNQX and D-APV, and inhibitory receptor blockers bicuculline and strychnine, perfusion of WIN (5 μmol/L) hardly changed the frequencies of evoked action potentials by a series of positive current injection (from +10 to +100 pA). Phase-plane plot analysis showed that both average threshold voltage for triggering action potential and delay time to reach threshold voltage were not affected by WIN. However, WIN significantly decreased +dV/dtmax and -dV/dtmax of action potentials, suggestive of reduced rising and descending velocities of action potentials. The effects of WIN were reversed by co-application of SR141716, a CB1R selective antagonist. Moreover, WIN did not influence resting membrane potential of RGCs with synaptic inputs being blocked. These results suggest that activation of CB1Rs may regulate intrinsic excitability of rat RGCs through modulating evoked action potentials.

Key words: Action potential; cannabinoid CB1 receptor; patch-clamp; retinal ganglion cell; spontaneous firing; WIN55212-2

收稿日期：　　录用日期：

通讯作者：王中峰　　E-mail: zfwang@fudan.edu.cn

引用本文：

蒋淑霞, 李倩, 王霄汉, 李芳, 王中峰. 大麻素CB1受体对大鼠视网膜神经节细胞诱发动作电位的作用[J]. 生理学报 2013; 65 (4): 355-362.

JIANG Shu-Xia, LI Qian, WANG Xiao-Han, LI Fang, WANG Zhong-Feng. Activation of cannabinoid CB1 receptors modulates evoked action potentials in rat retinal ganglion cells. Acta Physiol Sin 2013; 65 (4): 355-362 (in Chinese with English abstract).