Jin Wen-Zhe, Liu Heng, Wan Peng, Chu Chun-Ping, Qiu De-Lai
Cellular Function Research Center, Yanbian University, Yanji, Jilin Province, China; Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, Jilin Province, China; Department of Pain, Affiliated Hospital of Yanbian University, Yanji City, Jilin Province, China.
Cellular Function Research Center, Yanbian University, Yanji, Jilin Province, China; Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, Jilin Province, China.
Eur J Pharmacol. 2016 Oct 5;788:37-44. doi: 10.1016/j.ejphar.2016.05.027. Epub 2016 Jun 14.
We recently reported that propofol depressed facial stimulation-evoked gamma-aminobutyric acid (GABA) transmission at cerebellar molecular layer interneuron-Purkinje cell (PC) synapses in mice in vivo, but facilitated excitatory parallel fiber inputs onto PCs. Here, we examine the effects of propofol on cerebellar granule cell layer (GCL) responses to facial stimulation in urethane-anesthetized mice, using electrophysiological and pharmacological methods. Cerebellar surface perfusion of propofol (50-1000μM) facilitated field potentials evoked in the cerebellar GCL by air-puff stimulation of the ipsilateral whisker pad, shown by increases in the half-width and area under the curve (AUC) of the stimulus onset response (Ron). Propofol also significantly increased the amplitude of the stimulus offset response (Roff) and Roff/Ron ratio. The propofol-induced increase in Ron AUC was dose-dependent, with a 50% effective concentration (EC50) of 242.4µM. Application of the GABAA receptor antagonist gabazine (20μM) significantly increased the amplitude, half-width, rise tau and AUC of Ron, but these parameters were further increased by additional application of propofol (300µM). Notably, application of the N-methyl-d-aspartate (NMDA) receptor blocker D-APV (250µM) significantly attenuated the half-width and AUC of Ron and the amplitude of Roff, without significantly changing the amplitude of Ron. These results indicate that propofol enhanced facial stimulation-evoked responses in the cerebellar GCL via NMDA receptor activation, which resulted in the facilitation of excitatory parallel fiber inputs onto cerebellar PCs in mice in vivo.
我们最近报道，在体内实验中，丙泊酚可抑制小鼠小脑分子层中间神经元-浦肯野细胞（PC）突触处面部刺激诱发的γ-氨基丁酸（GABA）传递，但可促进PC上兴奋性平行纤维的输入。在此，我们使用电生理和药理学方法，研究丙泊酚对氨基甲酸乙酯麻醉小鼠小脑颗粒细胞层（GCL）对面部刺激反应的影响。通过同侧触须垫吹气刺激诱发小脑GCL中的场电位，小脑表面灌注丙泊酚（50-1000μM）可使其增强，刺激起始反应（Ron）的半峰宽和曲线下面积（AUC）增加。丙泊酚还显著增加了刺激终止反应（Roff）的幅度以及Roff/Ron比值。丙泊酚诱导的Ron AUC增加呈剂量依赖性，半数有效浓度（EC50）为242.4μM。应用GABAA受体拮抗剂荷包牡丹碱（20μM）可显著增加Ron的幅度、半峰宽、上升时间常数和AUC，但额外应用丙泊酚（300μM）可使这些参数进一步增加。值得注意的是，应用N-甲基-D-天冬氨酸（NMDA）受体阻滞剂D-APV（250μM）可显著减弱Ron的半峰宽和AUC以及Roff的幅度，但对Ron的幅度无显著影响。这些结果表明，丙泊酚通过激活NMDA受体增强了小脑GCL对面部刺激的反应，从而促进了体内小鼠小脑PC上兴奋性平行纤维的输入。
