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异丙酚对离体大鼠下丘脑视上核神经元的抑制作用

张环环, 汪萌芽^*

皖南医学院细胞电生理研究室，芜湖 241002

摘要

为了观察新型静脉全麻药异丙酚对下丘脑视上核(supraoptic nucleus, SON)神经元的作用，并分析其可能的离子机制，本研究应用细胞内记录技术，观察异丙酚灌流对成年雄性Sprague Dawley (SD)大鼠下丘脑冠状切片SON神经元膜电学性质和动作电位的影响。结果显示，0.1 mmol/L异丙酚使SON神经元静息电位显著降低(P < 0.01)，而0.3和1.0 mmol/L异丙酚显著缩短膜时间常数、减小斜率电阻(P < 0.01)。在超极化电流脉冲幅值大于0.5 nA时，部分(11/18) SON神经元可表现出超极化激活的阳离子通道(hyperpolarization-activated cation channel，Ih通道)所致的异常整流现象，而异丙酚能可逆地取消该异常整流现象。0.1 mmol/L异丙酚可显著提高SON神经元阈电位水平(P < 0.01)，显著降低最大上升斜率(Max L. slope) (P < 0.05)，而0.3和1.0 mmol/L异丙酚可完全取消部分(分别为1/18和12/17) SON神经元的动作电位。对于未被异丙酚完全取消动作电位的SON神经元，0.3 mmol/L异丙酚可显著降低锋电位的幅度(P < 0.05)。0.3~1.0 mmol/L异丙酚可显著抑制0.1~0.7 nA去极化电流时的神经元放电频率，使电流刺激强度-放电频率曲线右移和压低。以上结果提示，异丙酚可降低下丘脑SON神经元的兴奋性，其机制可能涉及对Ih通道和Na+通道的抑制。

关键词： 视上核; 异丙酚; 超极化激活的阳离子通道; 动作电位; 膜电位; 电生理学; 大鼠

分类号：R338

[Inhibitory effects of propofol on supraoptic nucleus neurons of rat hypothalamus in vitro.] [Article in Chinese]

ZHANG Huan-Huan, WANG Meng-Ya^*

Cell Electrophysiology Laboratory, Wannan Medical College, Wuhu 241002, China

Abstract

To investigate the effects of novel intravenous general anesthetic propofol on membrane electrophysiological characteristics and action potential (AP) of the supraoptic nucleus (SON) neurons and possible ionic mechanisms, intracellular recordings were conducted in SON neurons from the coronal hypothalamic slice preparation of adult male Sprague Dawley (SD) rats. The results showed that bath application of 0.1 mmol/L propofol induced a significant decline in resting potential (P < 0.01), and higher concentrations of propofol (0.3 and 1.0 mmol/L) decreased time constant and slope resistance of cell membrane (P < 0.01). Under the hyperpolarizing current pulses exceeding 0.5 nA, an anomalous rectification was induced by hyperpolarization-activated cation channel (Ih channel) in 11 out of 18 tested SON neurons. Bath of propofol reversibly decreased the anomalous rectification. Moreover, 0.1 mmol/L propofol elevated threshold level (P < 0.01) and decreased Max L. slope (P < 0.05) of the spike potential in SON neurons. Interestingly, 0.3 and 1.0 mmol/L propofol nullified APs in 6% (1/18) and 71% (12/17) tested SON neurons, respectively. In the SON neurons where APs were not nullified, propofol (0.3 mmol/L) decreased the amplitude of spike potential (P < 0.05). The higher concentrations of propofol (0.3 and 1.0 mmol/L) decreased firing frequencies evoked by depolarizing current pulses (0.1–0.7 nA), and shifted the current intensity-firing frequency relation curves downward and to the right. These results suggest that propofol decreases the excitability of SON neurons by inhibiting Ih and sodium channels.

Key words: supraoptic nucleus; propofol; hyperpolarization-activated cation channel; action potential; membrane potential; electrophysiology; rat

收稿日期：2011-10-15　　录用日期：2012-02-06

通讯作者：汪萌芽　　E-mail: wangmy@wnmc.edu.cn

引用本文：

张环环, 汪萌芽. 异丙酚对离体大鼠下丘脑视上核神经元的抑制作用[J]. 生理学报 2012; 64 (2): 163-169.

ZHANG Huan-Huan, WANG Meng-Ya. [Inhibitory effects of propofol on supraoptic nucleus neurons of rat hypothalamus in vitro.] [Article in Chinese]. Acta Physiol Sin 2012; 64 (2): 163-169 (in Chinese with English abstract).