Yang Chuan-Xiu, Xu Han, Zhou Ke-Qing, Wang Meng-Ya, Xu Tian-Le
School of Life Sciences, University of Science and Technology of China, Hefei, China.
Anesth Analg. 2006 Apr;102(4):1114-20. doi: 10.1213/01.ane.0000198657.76705.38.
To assess the actions of thiopental at the spinal dorsal horn level, we examined the effects of thiopental using the whole cell patch-clamp technique on mechanically dissociated rat spinal dorsal horn neurons. Thiopental, at large concentrations, elicited a current (I(Thio)) through activation of chloride conductance, and its threshold concentration was approximately 50 microM. I(Thio) was sensitive to bicuculline, a gamma-aminobutyric acid (GABA)A receptor antagonist, but not to strychnine, a glycine receptor antagonist. At a clinically relevant concentration (30 muM), thiopental markedly enhanced the peak amplitude of a subsaturating GABA-induced current (I(GABA)) but not that of a saturating GABA-induced current. Furthermore, thiopental prolonged the time constants of both desensitization and deactivation of I(GABA). At a large concentration (300 muM), it inhibited the peak amplitude of I(GABA), which may be the result of open-channel blockade. In addition, at 30 microM, thiopental increased the duration and decreased the frequency of GABAergic miniature inhibitory postsynaptic currents. These results indicate that thiopental enhances GABAergic inhibitory transmission and suggest that GABA(A) receptors in the spinal cord are a potential target through which thiopental causes immobility and depresses the response to noxious stimuli.
为了评估硫喷妥钠在脊髓背角水平的作用，我们使用全细胞膜片钳技术研究了硫喷妥钠对机械分离的大鼠脊髓背角神经元的影响。高浓度的硫喷妥钠通过激活氯电导引发电流（I(Thio)），其阈值浓度约为50μM。I(Thio)对γ-氨基丁酸（GABA）A受体拮抗剂荷包牡丹碱敏感，但对甘氨酸受体拮抗剂士的宁不敏感。在临床相关浓度（30μM）下，硫喷妥钠显著增强了亚饱和GABA诱导电流（I(GABA)）的峰值幅度，但对饱和GABA诱导电流的峰值幅度没有影响。此外，硫喷妥钠延长了I(GABA)脱敏和失活的时间常数。在高浓度（300μM）下，它抑制了I(GABA)的峰值幅度，这可能是开放通道阻断的结果。此外，在30μM时，硫喷妥钠增加了GABA能微小抑制性突触后电流的持续时间并降低了其频率。这些结果表明硫喷妥钠增强了GABA能抑制性传递，并提示脊髓中的GABA(A)受体是硫喷妥钠导致不动和抑制对有害刺激反应的潜在靶点。
