The mechanism of general anesthetics

全身麻醉药的作用机制

• 批准号: 13671618
• 负责人: KITAMURA Akira
• 金额: $ 2.18万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671618/
• 关键词: synaptic transmission; patch-clamp; halothane; propofol; GABA; シングルチャネルレコーディング; カルシウムイオンチャンネル; NMDA; AMPA

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.

我们研究了全身麻醉药对兴奋性和抑制性神经递质释放和突触后反应的作用机制。用全细胞和细胞贴附式膜片钳技术在大鼠皮层神经元上记录自发性微小抑制性和兴奋性突触后电流（mIPSC和mEPSC）。0.6 mM氟烷或0.3μM丙泊酚的应用延长了mIPSC的持续时间，并增加了每个自发突触事件期间的总电荷。氟烷还降低了mIPSC和微型非NMDA EPSC的频率。用特异性高压门控钙通道阻断剂的实验表明，氟烷阻断N型和P/Q型钙通道而不影响L型钙通道，从而导致兴奋性和抑制性神经递质释放的减少。细胞贴附膜片钳记录显示，每种药物的应用在单通道电导没有差异。斑片开放概率分析显示，每种药物的通道开放概率增加4至5倍，并表明氟烷增加它的平均开放时间，而丙泊酚减少爆发间期。氟烷和丙泊酚之间观察到的差异可能反映在不同的临床效果和使用。

项目成果

Kitamura A, et al.: "Effects of Halothane and Propofol on Excitatory and Inhibitory Synaptic Transmission in Rat Cortical Neurons"The Journal of Pharmacology and Experimental Therapeutics. 304. 162-171 (2003)

Kitamura A等人：“氟烷和异丙酚对大鼠皮质神经元兴奋性和抑制性突触传递的影响”药理学和实验治疗学杂志。

北村 晶: "ラット皮質ニューロンにおける抑制性シナプス伝達へのハロセン、プロポフォールの作用への考察"麻酔と蘇生. 37・3. 69-70 (2001)

Akira Kitamura：“氟烷和异丙酚对大鼠皮质神经元抑制性突触传递的影响的研究”麻醉与复苏 37・3（2001）。

Kitamura A, et al.: "Effects of Halothene and Propofol on Excitatory and Inhibitory Synaptic Transmissino in Rat Cortical Neurons"The Journal of Pharmacology and Experimental Tharapeutics. 304. 162-171 (2003)

Kitamura A等人：“氟乙烯和异丙酚对大鼠皮质神经元兴奋性和抑制性突触传递的影响”药理学和实验治疗学杂志。

Kitamura A.: "Effects of halothane and propofol on excitatory and inhibitory synaptic transmission in rat cortical neurons"The Journal of Pharmacology and Experimental Therapeutics. 304・1. 162-171 (2003)

Kitamura A.：“氟烷和异丙酚对大鼠皮质神经元的兴奋性和抑制性突触传递的影响”《药理学和实验治疗学杂志》304・1（2003）。

Kitamura A, et al.: "Halothane and Propofol Modulation of GABA_A Receptor-Mediated Inhibitory Postsynaptic Currents"Anesthesia and Resuscitation. 37. 69-70 (2001)

Kitamura A 等人：“GABA_A 受体介导的抑制性突触后电流的氟烷和异丙酚调节”麻醉和复苏。