Propofol and sevoflurane depress spinal neurons in vitro via different molecular targets
Propofol and sevoflurane depress spinal neurons in vitro via different molecular targets
复制标题
DOI：
10.1097/00000542-200411000-00017
复制
发表时间：
2004-11-01
期刊：
影响因子：
8.8
通讯作者：
Antkowiak, B
中科院分区：
文献类型：
--
作者：
Grasshoff, C;Antkowiak, B
背景：全身麻醉药产生不动的能力主要是由脊椎调节的。最近，有令人信服的证据表明，异丙酚的脊髓作用涉及γ-氨基丁酸A型(GABA(A))受体，而甘氨酸受体的作用尚不确定。目前常用的七氟醚麻醉剂在脊髓中的相关分子靶点尚不清楚，但间接证据表明其作用机制与异丙酚不同。方法：在培养的胚胎大鼠脊髓组织切片上，通过腹角间神经元细胞外电压记录，研究七氟醚和异丙酚对自发性动作电位放电的影响。结果：异丙酚和七氟醚减少了神经元自发性动作电位的放电。产生半最大效应的浓度(0.11 mU异丙酚，0.11 mM七氟醚)低于不动的半数有效浓度(1~1.5 mU异丙酚，0.35 mM七氟醚)。在较高浓度时，七氟醚可完全抑制动作电位活动，而异丙酚则不能。七氟醚的作用主要由甘氨酸受体(45%)和GABA(A)受体(38%)介导，而异丙酚几乎完全通过GABA(A)受体(96%)起作用。结论：甘氨酸和GABA(A)受体是七氟醚脊髓内介导抑制作用的最重要的分子靶点。他们提供的证据表明，七氟醚通过一种不同于静脉麻醉剂异丙酚的作用机制导致不动。在作者的研究中，异丙酚仅通过GABA(A)受体起作用的发现可以解释其抑制脊髓神经元的有限能力。
Background: The capacity of general anesthetics to produce immobility is primarily spinally mediated. Recently, compelling evidence has been provided that the spinal actions of propofol involve gamma-aminobutyric acid type A(GABA(A)) receptors, whereas the contribution of glycine receptors remains uncertain. The relevant molecular targets of the commonly used volatile anesthetic sevoflurane in the spinal cord are largely unknown, but indirect evidence suggests a mechanism of action distinct from propofol.Methods: The effects of sevoflurane and propofol on spontaneous action potential firing were investigated by extracellular voltage recordings from ventral horn interneurons; in cultured spinal cord tissue slices obtained from embryonic rats (embryonic days 14-15).Results: Propofol and sevoflurane reduced spontaneous action potential firing of neurons. Concentrations causing half-maximal effects (0.11 mum propofol, 0.11 mm sevoflurane) were lower than the median effective concentration immobility (1-1.5 mum propofol, 0.35 mm sevoflurane). At higher concentrations, complete inhibition of action potential activity was observed with sevoflurane but not with propofol. Effects of sevoflurane were mediated predominantly by glycine receptors (45%) and GABA(A) receptors (38%), whereas propofol acted almost exclusively via GABA(A) receptors (96%).Conclusions: The authors' results suggest that glycine and GABA(A) receptors are the most important molecular targets mediating depressant effects of sevoflurane in the spinal cord. They provide evidence that sevoflurane causes immobility by a mechanism distinct from the actions of the intravenous anesthetic propofol. The finding that propofol acts exclusively via GABA(A) receptors can explain its limited capacity to depress spinal neurons in the authors' study.