咪达唑仑对交感神经元电压门控性钾电流的影响

中国临床药理学与治疗学 ›› 2002, Vol. 7 ›› Issue (3): 197-199.

咪达唑仑对交感神经元电压门控性钾电流的影响

茆庆洪, 庄心良, 陈猛, 唐俊, 徐国辉

上海市第一人民医院麻醉科, 上海 200080

收稿日期:2002-03-31 修回日期:2002-04-13 发布日期:2020-12-01
通讯作者: 茆庆洪, 男, 博士, 从事麻醉药理学研究。Tel:021-63240090-8101 E-mail:maoqinghong@citiz.net
作者简介:庄心良, 男, 教授, 博士生导师。

Effects of midazolam on macroscopic voltage-gated potassium currents in rat sympathetic neurons

MAO Qing-Hong, ZHUANG Xin-Liang, CHEN Meng, TANG Jun, XU Guo-Hui

Department of Anesthesiology, Shanghai First People's Hospital, Shanghai 200080, China

Received:2002-03-31 Revised:2002-04-13 Published:2020-12-01

摘要/Abstract

摘要： 目的: 观察不同浓度咪达唑仑对交感神经元电压门控钾通道电流的影响, 探讨临床浓度咪达唑仑对钾电流的作用是否与抑制交感神经系统有关。方法: 用酶消化法获得急性分离的SD 大鼠(7 ~ 10 d) 颈上交感神经节细胞, 应用膜片钳技术记录不同浓度的咪达唑仑对电压门控钾电流的影响。结果: 在钳制电位(Vh)-80 mV, 刺激电压(Vt)^-100 mV ~ 30 mV, 时程160 ms 条件下, 不同浓度的咪达唑仑对电压门控钾电流均有抑制作用, 且呈浓度依赖性。临床相关浓度的咪达唑仑(0.3 μmol·L^-1) 使钾通道电流峰值下降3.89 %(P =0.88) 。50 %钾通道电流峰值受抑制时的咪达唑仑浓度(IC₅₀) 约为70.06 μmol·L^-1 。结论: 咪达唑仑对交感神经元电压门控钾电流具浓度依赖性抑制作用, 但临床浓度咪达唑仑对钾电流影响较小。

关键词: 咪达唑仑, 颈上交感神经节, 电压门控性钾通道

Abstract: AIM: To explore the influence of different concentration midazolam on the macroscopic voltage-gated potassium currents and to discuss the relationship between potassium currents andinhibitory effect of clinical relevant concentration midazolam on sympathetic nervous system.METHODS: Superior sympathetic ganglion neurons were dissociated enzymatically from 7 to10-day-old rat.Experiments were performed about 5 h after plating atroom temperature (20-24 ℃).Appropriate solution was chosen to separate the K⁺ current from the other transmembrane currents.1 μmol·L^-1 TTX was applied to the extracelluar solution to block the Na + current.Midazolam was also resolvedin extracelluar solution to get various concentration (0.1, 0.3, 3, 10, 50, 100 μmol·L^-1).Currents were recorded with the patch-clamp technique in whole cell configuration using glass electrodes with a tip resistance of 2-4 M.Potassium currents were evoked by test pulse from^-100 mV to +30 mV with holding potential-80mV. Data were analyzed using Clampfit 6.0 and Oringih 5.0 software.Whole-cell current records were corrected for leakage and capacitance by using the P/5 protocol.RESULTS: Midazolam dose-dependently inhibited the wholecell potassium currents.Clinical relevant concentrationmidazolam (0.3 μmol·L^-1) only reduced the peak currents by 3.89 %(P =0.88).The concentration required to produce 50 %current inhibition(IC₅₀) was 76.065 μmol·L^-1.CONCLUSION: Midazolam inhibits the whole-cell potassium current significantly and dose-dependently, but clinical relevant concentration midazolam has minor effect on the potassium currents, indicating that the inhibitory effect of midazolam on potassium current is not related to the suppression of activity of sympathetic system.

Key words: midazolam, superior cervical ganglion, potassium current

中图分类号:

R965

茆庆洪, 庄心良, 陈猛, 唐俊, 徐国辉. 咪达唑仑对交感神经元电压门控性钾电流的影响[J]. 中国临床药理学与治疗学, 2002, 7(3): 197-199.

MAO Qing-Hong, ZHUANG Xin-Liang, CHEN Meng, TANG Jun, XU Guo-Hui. Effects of midazolam on macroscopic voltage-gated potassium currents in rat sympathetic neurons[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2002, 7(3): 197-199.

参考文献

1 Kawamoto M, Shimokawa A, Takasaki M.Effects of midazolam on heart rate variability during surgery under spinal anaesthesia [J].Anaesth Intensive Care, 1995;23:464-8
2 Komatsu T, singh PK, Kimura T, et al.Differential effects of ketamine and midazolam on heart rate variability [J].Can J Anaesth, 1995;42:1003-9
3 Marty J, Gauzit R, Lefevre P, et al.Effects of diazepam and midazolam on baroreflexcontrol of heart rate and on sympathetic activity in humans[J].Anesth Analg, 1986;65:113-9
4 郑吉建, 庄心良, 刘宝刚, 等.咪唑安定对交感神经元全细胞钠通道电流的抑制作用[J].中国临床药理学与治疗学, 2000;5:108-11
5 Hille B.Ionic channels in excitable membranes.Sunderland, MA, Sinaurer Associates, 19926.Safronov BV, Bischoff U, VogelW. Single voltage-gated K⁺ channels and their functions in small dorsal root ganglion neurones of rat[J].J Physiol, 1996; 493:393-408
6 Reyes AD, Rubel EW, Spain WJ.Membrane properties underlying the firing of neurons in the avian cochlear nucleus[J].J Neurosci, 1994;14:5352-64
7 Brew HM, Forsythe ID.Two voltage-dependent K⁺ conductances with complementary functions in postsynaptic integration at a central auditory synapse[J].J Neurosci, 1995;15:8011-22
8 Nakagawa T, Komune S, Vemura T, et al.Excitatory amino acid response in isolated spinal ganglion cells of guinea pig cochlea[J].J Neurophysiol, 1991;65:715-23
9 Schofield GG, Ikeda SR.Sodium and calcium currents of acutely isolated adultrat superior cervical ganglion neurons[J].Pflugers Arch, 1988;411:481-90
10 Huang R, Somjen GG.Effects of hypertonia on voltage-gatedion currents in freshly isolated hippocampal neurons,on synaptic currents in neurons in hippocampal slices[J].Brain Res, 1997; 14, 748:157-67
11 何湘平, 刘青松, 谢佐平, 等.培养的新生大鼠交感神经元膜电学性质及电压门控通道的膜片钳研究[J].生理学报, 1995;47:441-7.
12 施卫星, 孙月明.电压门控离子通道的药理[A].见:邹冈主编.基础神经药理学[M].第2 版.北京:科学技术出版社, 1999;378.
13 Marsh SJ, Brown DA.Potassium currents contributing to action potential repolarization in dissociated cultured rat superior cervical sympathetic neurons[J].Neurosci Lett, 1991;133:298-302
14 Ireland DR, Davies PJ, McLachlan EM.The role of N-type Ca²⁺ channels in regulating excitability of guinea-pig sympathetic neurons[J].J Auton Nerv Syst, 1998;73:109-14.
15 Schofield GG, Ikeda SR.Potassium currents of acutely isolated adultrat superior cervical ganglion neurons[J].Brain Research, 1989;485:205-14.
16 Hirning LD, Fox AP, McCleskey EW, et al.Dominantrole of N-type Ca²⁺ channels in evoked release of norepinephrine from sympathetic neurons[J].Science, 1988;239:57-60.
17 Carrier GO.Whole-cell and perforated patchrecording offour distinct K⁺ currents in acutely dispersed celiac-superior mesenteric ganglia neurons of adultrats[J].Brain Research, 1995; 701:1-12.
18 Friederich P, Urban BW.Interaction of intravenous anesthetics with human neuronal potassium currents in relation to clinical concentrations[J].Anesthesiology, 1999;91:1853-60.

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