The mechanism of general anesthetics

我们研究了全身麻醉剂对兴奋和抑制系统中递质释放和突触后反应的作用机制。利用全细胞和贴壁膜片钳技术记录了大鼠皮层神经元突触网络中自发的微型抑制性和兴奋性突触后电流（mIPSCs和mEPSCs）。0.6 mM氟烷或0.3μM异丙酚均能延长mIPSCs的持续时间，提高每次自发突触事件的总电荷。氟烷还降低了mIPSC和微型非nmda EPSCs的频率。使用高压门控钙通道阻滞剂的实验表明，氟烷阻断n型和P/Q型钙通道，但对l型钙通道没有影响，从而导致兴奋性和抑制性神经递质的释放减少。细胞贴附膜片钳记录显示，每种药物的单通道电导没有差异。膜片打开概率分析显示，每种药物的通道打开概率增加了4 ~ 5倍，并且表明氟烷随着平均打开寿命的延长而增加，而异丙酚则随着间隔时间的缩短而增加。氟烷和异丙酚之间的差异可能反映在不同的临床效果和用法上。

We studied the mechanism of action of general anesthetics on transmitter release and postsynaptic responses in both excitatory and inhibitory systems. Spontaneous miniature inhibitory and excitatory postsynaptic currents (mIPSCs and mEPSCs) were recorded with whole-cell and cell-atached patch-clamp techniques in rat cortical neurons established synaptic networks. The application of 0.6 mM halothane or 0.3μM propofol prolonged the duration of mIPSCs and enhanced the total charge during each spontaneous synaptic event. Halothane also decreased the frequency of mIPSC and miniature non-NMDA EPSCs. Experiments using specific high voltage-gated calcium channel blockers indicated that halothane blocked N-type and P/Q type calcium channels without effect on L-type calcium channels, thus leading to a decrease in the release of both excitatory and inhibitory neurotransmitters. Cell-attached patch-clamp recordings revealed no differences in single-channel conductance by application of each drug. Analysis of patch open probability revealed 4- to 5-fold increase in the open probability of channels on each drug, and indicated that halothane increased it with increasing the mean open life time, meanwhile propofol did with decreasing the interburst interval. The observed differences between halothane and propofol may be reflected in different clinical effects and usage.