异丙酚对海马锥体神经元钠通道电流的抑制作用

Suppression of sodium channel currents in rat hippocampal pyramidal neurons by propofol

目的 研究异丙酚对海马锥体神经元钠通道电流的影响,探讨脑钠通道在异丙酚麻醉中的作用。方法 酶消化法急性分离SD大鼠(10～14 d)海马锥体神经元,全细胞膜片钳技术记录异丙酚和脂肪乳剂对其钠通道电流的影响。结果 在钳制电位-100 mV时,4组浓度(10、30、50、100μmol/L)的异丙酚分别抑制峰钠电流为:14.4％±8.7％、42.9％±8.8％、67.2％±18.1％和85.1％±14.9％,抑制程度与浓度呈正相关(r=0.993,P<0.01),IC50为32.5 μmol/L。与本研究中较高浓度异丙酚组(50和100μmol/L)对应浓度的脂肪乳剂(ILP50组和ILP100组)对峰钠电流无明显影响。结论异丙酚对脑钠通道电流有明显的抑制作用,且呈剂量依赖性,提示脑钠通道的抑制在异丙酚的麻醉中可能起一定作用。

Objective To investigate the effect of propofol on the whole-cell sodium currents in rat hippocampal pyramidal neurons in order to determine whether brain sodium channels are involved in the molecular mechanism of action of propofol. Methods The pyramidal neurons were enzymatically isolated from rat hippocampus. The experiment was divided into seven groups: in group 1-4 (propofol groups) different amount of propofol (dissolved in intralipid) was added to bath solution and four solutions of different propofol concentration-10, 30, 50 and 100 μmol·L-1 were prepared (Pro10 , Pro30 , Pro50 and Pro100 ); in group 5-6 intralipid alone (without propofol) was added to bath solution and two solutions of intralipid concentration equal to that of Pro50 and Pro100 were prepared; in group 7 neither propofol nor intralipid was added to the bath solution. The effect of propofol and intralipid on the whole-cell sodium channel currents were assessed using patch-clamp technique.Results When the holding potential was - 100 mV, the four concentrations of propofol (10, 30, 50 and 100 μmol·L-1) reduced peak sodium currents by 14.4%±8.7% , 42.9%±8.8% , 67.2±18.1% and 85.1%±14.9% respectively, with a mean LC50 of 32.5 μmol·L-1.The two concentrations of intralipid did not significantly affect the peak sodium currents. Conclusion Propofol significantly inhibits the brain sodium channel currents in a dose-dependent manner, indicating a possible role of brain sodium channel suppression in propofol anesthesia.