异丙酚对离体视上核神经元兴奋性突触传递的抑制作用
张环环, 郑超, 王邦安, 汪萌芽*
皖南医学院细胞电生理研究室,芜湖 241002
摘要
为了解静脉全麻药异丙酚对视上核神经元兴奋性突触传递的作用并分析其可能机制,本研究采用细胞内记录技术,观察异丙酚(0.1~3.0 mmol/L)对下丘脑冠状切片视上核(supraoptic nucleus, SON)神经元突触后电位(postsynaptic potential, PSP)的作用。结果显示,在局部电刺激SON背外侧区域可诱发PSP的8个细胞中,异丙酚能浓度依赖性降低88%细胞的PSP幅度(P < 0.01)、曲线下面积、时程、半幅时程和10%~90%衰减时间(P < 0.05)。1.0 mmol/L异丙酚能可逆地完全取消29% (2/7)细胞的PSP。压力喷射外源性谷氨酸在SON神经元诱发伴有膜电阻减小的去极化反应,异丙酚对谷氨酸反应呈可逆的浓度依赖性抑制,但0.3 mmol/L异丙酚仅完全取消同步记录的PSP,却未能完全抑制谷氨酸反应。用GABAA受体阻断剂印防己毒素(30 µmol/L)预处理后,7个细胞兴奋性突触后电位(excitatory postsynaptic potential, EPSP)增大,再灌流异丙酚后观察到异丙酚对EPSP的抑制作用减弱。结果提示,异丙酚抑制SON神经元兴奋性突触传递的作用可能同时涉及突触前和突触后机制。在突触后可能通过激活GABAA受体而抑制SON神经元的兴奋性突触传递,但高浓度的异丙酚也可能涉及对兴奋性谷氨酸受体的直接抑制。
关键词: 异丙酚; 视上核; 兴奋性突触后电位; GABAA受体; 谷氨酸受体
分类号:R338
Inhibitory effects of propofol on excitatory synaptic transmission in supraoptic nucleus neurons in vitro
ZHANG Huan-Huan, ZHENG Chao, WANG Bang-An, WANG Meng-Ya*
Cell Electrophysiology Laboratory, Wannan Medical College, Wuhu 241002, China
Abstract
The present study was designed to investigate the inhibitory effects of intravenous general anesthetic propofol (0.1–3.0 mmol/L) on excitatory synaptic transmission in supraoptic nucleus (SON) neurons of rats, and to explore the underlying mechanisms by using intracellular recording technique and hypothalamic slice preparation. It was observed that stimulation of the dorsolateral region of SON could elicit the postsynaptic potentials (PSPs) in SON neurons. Of the 8 tested SON neurons, the PSPs of 7 (88%, 7/8) neurons were decreased by propofol in a concentration-dependent manner, in terms of the PSPs’ amplitude (P < 0.01), area under curve, duration, half-width and 10%–90% decay time (P < 0.05). The PSPs were completely and reversibly abolished by 1.0 mmol/L propofol at 2 out of 7 tested cells. The depolarization responses induced by pressure ejection of exogenous glutamate were reversibly and concentration-dependently decreased by bath application of propofol. The PSPs and glutamate-induced responses recorded simultaneously were reversibly and concentration-dependently decreased by propofol, but 0.3 mmol/L propofol only abolished PSPs. The excitatory postsynaptic potentials (EPSPs) of 7 cells increased in the condition of picrotoxin (30 µmol/L, a GABAA receptor antagonist) pretreatment. On this basis, the inhibitory effects of propofol on EPSPs were decreased. These data indicate that the presynaptic and postsynaptic mechanisms may be both involved in the inhibitory effects of propofol on excitatory synaptic transmission in SON neurons. The inhibitory effects of propofol on excitatory synaptic transmission of SON neurons may be related to the activation of GABAA receptors, but at a high concentration, propofol may also act directly on glutamate receptors.
Key words: Propofol; supraoptic nucleus; excitatory postsynaptic potentials; receptors, GABAA; receptors, glutamate
收稿日期:2015-05-26 录用日期:2015-08-18
通讯作者:汪萌芽 E-mail: wangmy@wnmc.edu.cn
引用本文:
张环环, 郑超, 王邦安, 汪萌芽. 异丙酚对离体视上核神经元兴奋性突触传递的抑制作用[J]. 生理学报 2015; 67 (6): 583-590.
ZHANG Huan-Huan, ZHENG Chao, WANG Bang-An, WANG Meng-Ya. Inhibitory effects of propofol on excitatory synaptic transmission in supraoptic nucleus neurons in vitro. Acta Physiol Sin 2015; 67 (6): 583-590 (in Chinese with English abstract).