咪达唑仑对大鼠颈上交感神经节细胞乙酰胆碱受体通道的影响

中国临床药理学与治疗学 ›› 2011, Vol. 16 ›› Issue (7): 749-753.

咪达唑仑对大鼠颈上交感神经节细胞乙酰胆碱受体通道的影响

张成密¹, 沈浩², 徐子锋², 王莹恬², 俞卫锋¹, 郑吉建²

¹第二军医大学东方肝胆外科医院麻醉科,上海 200438;
²上海市第一人民医院麻醉科,上海 200080

收稿日期:2011-04-22 修回日期:2011-05-31 出版日期:2011-07-26 发布日期:2011-09-22
通讯作者: 郑吉建,医学博士,硕士生导师,研究方向:麻醉电生理。Tel: 021-37798758 E-mail: zhengjijian2009@gmail.com
作者简介:张成密,男,硕士研究生,研究方向:麻醉电生理。

Effects of midazolam on acetylcholine receptor channels in rat superior cervical ganglion neurons

ZHANG Cheng-mi¹, SHEN Hao², XU Zi-feng², WANG Ying-tian², YU Wei-feng¹, ZHENG Ji-jian²

¹Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China;
²Department of Anesthesiology, Shanghai First People's Hospital, Shanghai 200080, China

Received:2011-04-22 Revised:2011-05-31 Online:2011-07-26 Published:2011-09-22

摘要/Abstract

摘要： 目的: 研究咪达唑仑(Midazolam)对SD大鼠颈上交感神经节细胞乙酰胆碱受体(AChR)通道的影响,以探讨其循环抑制机制。方法: 酶消化法急性分离SD大鼠(7~10 d)颈上交感神经节细胞,全细胞膜片钳技术记录咪达唑仑对AChR通道电流的影响。结果: 在钳制电压(V_h) -60 mV 条件下,氯化乙酰胆碱可激发一快速激活且快速衰减的内向电流即AChR通道电流,其半数有效剂量(EC₅₀)为 39.65 μmol/L;临床相关浓度的咪达唑仑(0.3 μmol/L)使 200 μmol/L 氯化乙酰胆碱激发的AChR通道电流峰值降低 23.41% (P<0.05,n=6),而通道的脱敏感衰减速率却由 45.59%±14.21%增加至 57.93%±13.74% (P<0.01,n=6)。随浓度增加,咪达唑仑抑制AChR通道电流和加速AChR通道脱敏感的作用也逐渐增强。咪达唑仑抑制AChR通道电流,但并不改变AChR通道的反转电位,且在膜电位-20 mV 至-70 mV 之间,其抑制作用为电压非依赖性。结论: 临床相关浓度的咪达唑仑对交感神经节全细胞AChR通道电流有明显的抑制作用,呈浓度依赖性和电压非依赖性;其抑制作用主要与加快AChR通道的脱敏感衰减速率有关。

关键词: 麻醉, 咪达唑仑, 神经节, 交感, 膜片钳, 乙酰胆碱受体通道

Abstract: AIM: To study the effects of midazolam on the acetylcholine receptor (AChR) channels in rat superior cervical ganglion (SCG) neurons and the mechanisms of midazolam-induced hypotension.METHODS: Whole-cell patch-Clamp recordings were made from enzymatically isolated rat SCG neurons.RESULTS: At a holding potential (V_h) -60 mV, acetylcholine chloride evoked an inward current of rapid activation and then rapid desensitization decay, which was AChR channel currents, the half effective activation concentration (EC₅₀) was 39.65 μmol/L. Clinically relevant concentration of midazolam (0.3 μmol/L) inhibited the 200 μmol/L acetylcholine chloride-evoked macroscopic peak currents by 23.41% (P<0.05, n=6), enhanced the rates of desensitization from 45.59%±14.21% to 57.93%±13.74% (P<0.01, n=6), and these effects were dose dependent. Midazolam inhibited ACh-induced currents, but it did not alter the reversal potential of AChR channel. This inhibition was also voltage-independent at member potentials between -20 mV and -70 mV.CONCLUSION: Clinically relevant concentration of midazolam has significant inhibition on the AChR channel currents in rat sympathetic neurons; this inhibition is dos-dependent and voltage-independent, it is relevant to the desensitization of AChR channel.

Key words: Anesthesia, Midazolam, Patch-Clamp, AChR channel, Sympathetic ganglion

中图分类号:

R965.2

张成密, 沈浩, 徐子锋, 王莹恬, 俞卫锋, 郑吉建. 咪达唑仑对大鼠颈上交感神经节细胞乙酰胆碱受体通道的影响[J]. 中国临床药理学与治疗学, 2011, 16(7): 749-753.

ZHANG Cheng-mi, SHEN Hao, XU Zi-feng, WANG Ying-tian, YU Wei-feng, ZHENG Ji-jian. Effects of midazolam on acetylcholine receptor channels in rat superior cervical ganglion neurons[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(7): 749-753.

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