依托咪酯对腹外侧视前区神经元GABA能传递的抑制作用
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摘要
目的:研究依托咪酯对大鼠腹外侧视前区神经元γ-氨基丁酸能传递的影响。方法:大鼠腹外侧视前区切片,全细胞膜片钳记录神经元抑制性突触后电流。结果:依托咪酯(0.1μmol/L)可逆性地降低腹外侧视前区神经元的诱发抑制性突触后电流幅度,但未能显著性改变其配对脉冲比率。依托咪酯(0.1μmol/L)作用下,自发抑制性突触后电流的频率与幅度均显著性下降,其动力学参数未受影响。结论:依托咪酯可作用于突触前及突触后γ-氨基丁酸受体而抑制对腹外侧视前区神经元的γ-氨基丁酸能传递,这一作用可能使其处于兴奋状态,进而抑制结节乳头体核的组胺能神经元,减少组胺释放而发挥麻醉镇静作用。
Objective:To study the effect of etomidate on GABAergic transmission in neurons of rat ventrolateral preoptic(VLPO)area.Methods:Rat ventrolateral preoptic area slices were pre pared.Inhibitory postsynaptic current(IPSC)were investigated using whole-cell patch-clamp re cording in VLPO neurons.Results:Etomidate(0.1 μmol/L)reversibly decreased the amplitude of evoked IPSC in VLPO neurons,without changing its paired-pulse ratio(PPR).Etomidate(0.1 μmol/L)decreased the frequency and amplitude of spontaneous IPSC,did not induce appreciable change in the kinetics of the spontaneous IPSC.Conclusion:Etomidate may act presynaptically and postsynaptically to suppress GABAergic transmission to VLPO neurons,this effect may excite these neurons,lead to the inhibition of histaminergic neurons in tuberomamillary nucleus,which will de crease releasing of histamine and result in anesthesia and sedation.
Objective:To study the effect of etomidate on GABAergic transmission in neurons of rat ventrolateral preoptic(VLPO)area.Methods:Rat ventrolateral preoptic area slices were pre pared.Inhibitory postsynaptic current(IPSC)were investigated using whole-cell patch-clamp re cording in VLPO neurons.Results:Etomidate(0.1 μmol/L)reversibly decreased the amplitude of evoked IPSC in VLPO neurons,without changing its paired-pulse ratio(PPR).Etomidate(0.1 μmol/L)decreased the frequency and amplitude of spontaneous IPSC,did not induce appreciable change in the kinetics of the spontaneous IPSC.Conclusion:Etomidate may act presynaptically and postsynaptically to suppress GABAergic transmission to VLPO neurons,this effect may excite these neurons,lead to the inhibition of histaminergic neurons in tuberomamillary nucleus,which will de crease releasing of histamine and result in anesthesia and sedation.
引文
[1]Nelson L E,Guo T Z,Lu J,et al.The sedative compo nent of anesthesia is mediated by GABA(A)receptors in an endogenous sleep pathway[J].Nature neurosci ence,2002,5(10):979-984.
[2]Gallopin T,Fort P,Eggermann E,et al.Identification of sleep-promoting neurons in vitro[J].Nature,2000,404(6781):992-995.
[3]Liu Y W,Li J,Ye J H.Histamine regulates activities of neurons in the ventrolateral preoptic nucleus[J].J Physiol,2010,588(Pt21):4103-4116.
[4]Chan C M,Mitchell A L,Shorr A F.Etomidate is asso ciated with mortality and adrenal insufficiency in sep sis:A meta-analysis[J].Crit Care Med,2012,[Epub ahead].
[5]Garcia P S,Kolesky S E,Jenkins A.General Anesthet ic Actions on GABAA Receptors[J].Curr Neurophar macol,2010,8(1):2-9.
[6]Vanlersberghe C,Camu F.Etomidate and other non-barbiturates[J].Handb Exp Pharmacol,2008,(182):267-282.
[7]张敏,范坤,邵玉峰,等.依托咪酯经腹外侧视前核γ-氨基丁酸能神经元产生促眠作用[J].兰州大学学报:医学版,2011,37(1):1-5,10.
[8]Saper C B,Scammell T E,Lu J.Hypothalamic regula tion of sleep and circadian rhythms[J].Nature,2005,437(7063):1257-1263.
[2]Gallopin T,Fort P,Eggermann E,et al.Identification of sleep-promoting neurons in vitro[J].Nature,2000,404(6781):992-995.
[3]Liu Y W,Li J,Ye J H.Histamine regulates activities of neurons in the ventrolateral preoptic nucleus[J].J Physiol,2010,588(Pt21):4103-4116.
[4]Chan C M,Mitchell A L,Shorr A F.Etomidate is asso ciated with mortality and adrenal insufficiency in sep sis:A meta-analysis[J].Crit Care Med,2012,[Epub ahead].
[5]Garcia P S,Kolesky S E,Jenkins A.General Anesthet ic Actions on GABAA Receptors[J].Curr Neurophar macol,2010,8(1):2-9.
[6]Vanlersberghe C,Camu F.Etomidate and other non-barbiturates[J].Handb Exp Pharmacol,2008,(182):267-282.
[7]张敏,范坤,邵玉峰,等.依托咪酯经腹外侧视前核γ-氨基丁酸能神经元产生促眠作用[J].兰州大学学报:医学版,2011,37(1):1-5,10.
[8]Saper C B,Scammell T E,Lu J.Hypothalamic regula tion of sleep and circadian rhythms[J].Nature,2005,437(7063):1257-1263.