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,0.1mmol/L异丙酚使SON神经元静息电位显著降低(P〈0.01),而0.3和1.0mmol/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0.5nA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。0.1mmol/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1.0mmol/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,0.3mmol/L异丙酚可显著降低锋电位的幅度(P〈0.05)。0.3~1.0mmol/L异丙酚可显著抑制0.1~0.7nA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。
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 con-ducted 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 neu-rons by inhibiting Ih and sodium channels.