Key Laboratory of Cellular Function and Pharmacology of Jilin Province, Yanbian University, Yanji, Jilin Province, China; Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, Jilin Province, China; Department of Neurology, Affiliated Hospital of Yanbian University, Yanji, Jilin Province, China.
Key Laboratory of Cellular Function and Pharmacology of Jilin Province, Yanbian University, Yanji, Jilin Province, China; Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, Jilin Province, China.
Eur J Pharmacol. 2019 Jan 15;843:126-133. doi: 10.1016/j.ejphar.2018.11.022. Epub 2018 Nov 18.
Nicotinic acetylcholine receptors are cationic channels that mediate fast excitatory transmission in the central nervous system. Several nicotinic acetylcholine receptor subunits have been detected within cerebellar granule cell layer (GCL), and activation of these receptors may have a significant influence on neuronal synaptic transmission of the cerebellum. The aim of present study was to better understand the roles of nicotinic acetylcholine receptors during the sensory stimulation-evoked synaptic transmission in the cerebellar GCL. Our results showed that cerebellar surface perfusion of nicotine significantly facilitated the cerebellar GCL field potential responses evoked by air-puff stimulation of ipsilateral whisker pad, which exhibited increases in amplitude and area under the curve (AUC) of both stimulus onset responses (N1) and stimulus offset responses (N2). The nicotine-induced increase in AUC of facial stimulation-evoked N1 was dose-dependent with a 50% effective concentration (EC) of 32.6 μM. Application of either a selective α4β2 nicotinic acetylcholine receptors antagonist, DHβE (1 μM) or a selective α7 nicotinic acetylcholine receptors antagonist, MLA (1 μM) alone attenuated, but not completely abolished the nicotine-induced increases in the amplitude and AUC of the facial stimulation-evoked N1. However, simultaneous blockade of α7 and α4β2 nicotinic acetylcholine receptor subunits abolished the nicotine-induced increase in the amplitude of N1. These results indicate that nicotine activates α7 and α4β2 nicotinic acetylcholine receptor subunits, resulting in an enhancement of facial stimulation-evoked responses in mouse cerebellar GCL. Our results suggest that nicotine modulates the sensory information processing in the cerebellar GCL through α7 and α4β2 subunits nicotinic acetylcholine receptors.
烟碱型乙酰胆碱受体是阳离子通道，介导中枢神经系统中的快速兴奋传递。已经在小脑颗粒细胞层 (GCL) 中检测到几种烟碱型乙酰胆碱受体亚基，这些受体的激活可能对小脑神经元突触传递有重大影响。本研究旨在更好地了解烟碱型乙酰胆碱受体在小脑 GCL 感觉刺激诱发的突触传递中的作用。
我们的结果表明，小脑表面灌流尼古丁可显著促进由同侧触须垫气吹刺激引起的小脑 GCL 场电位反应，其表现为刺激起始反应 (N1) 和刺激结束反应 (N2) 的幅度和曲线下面积 (AUC) 增加。尼古丁诱导的面部刺激诱发 N1 的 AUC 增加呈剂量依赖性，半数有效浓度 (EC) 为 32.6 μM。单独应用选择性 α4β2 烟碱型乙酰胆碱受体拮抗剂 DHβE(1 μM)或选择性 α7 烟碱型乙酰胆碱受体拮抗剂 MLA(1 μM)可减弱，但不能完全消除尼古丁诱导的面部刺激诱发 N1 幅度和 AUC 的增加。然而，同时阻断 α7 和 α4β2 烟碱型乙酰胆碱受体亚基可消除尼古丁诱导的 N1 幅度增加。
这些结果表明，尼古丁激活 α7 和 α4β2 烟碱型乙酰胆碱受体亚基，导致小鼠小脑 GCL 中面部刺激诱发反应增强。我们的结果表明，尼古丁通过 α7 和 α4β2 烟碱型乙酰胆碱受体亚基调节小脑 GCL 中的感觉信息处理。
