Differential modulation of human N-methyl-D-aspartate receptors by structurally diverse general anesthetics
Differential modulation of human N-methyl-D-aspartate receptors by structurally diverse general anesthetics
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DOI：
10.1213/01.ane.0000204252.07406.9f
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发表时间：
2006-05-01
影响因子：
5.7
通讯作者：
Raines, DE
中科院分区：
文献类型：
--
作者：
Solt, K;Ii, EIE;Raines, DE
n -甲基- d -天冬氨酸（NMDA）受体被认为在兴奋性突触传递和伤害性通路中起作用。虽然先前的研究发现吸入麻醉剂在临床相关浓度下抑制NMDA受体介导的电流，但使用不同的实验方案，受体亚型和/或组织来源混淆了吸入麻醉剂对NMDA受体抑制能力的定量比较。在本研究中，我们试图通过使用双电极电压钳技术来确定不同临床和芳香吸入麻醉剂对非洲爪蟾卵母细胞中表达的人类NMDA受体NR1/NR2B亚型的抑制程度来填补这一空白。在最低肺泡麻醉浓度（MAC）下，麻醉化合物可逆地抑制NMDA受体电流12 +/- 6%至74 +/- 6%。这些结果表明，吸入麻醉药的等麻醉浓度在抑制NMDA受体的程度上可以有很大的不同。这种差异可能有助于确定这种受体在产生全身麻醉剂的体内作用中所起的作用。
N-Methyl-D-aspartate (NMDA) receptors have a presumed role in excitatory synaptic transmission and nociceptive pathways. Although previous studies have found that inhaled anesthetics inhibit NMDA receptor-mediated currents at clinically relevant concentrations, the use of different experimental protocols, receptor subtypes, and/or tissue sources confounds quantitative comparisons of the NMDA receptor inhibitory potencies of inhaled anesthetics. In the present study, we sought to fill this void by defining, using the two-electrode voltage-clamp technique, the extent to which diverse clinical and aromatic inhaled anesthetics inhibit the NR1/NR2B subtype of the human NMDA receptor expressed in Xenopus laevis oocytes. At 1 minimum alveolar anesthetic concentration (MAC), anesthetic compounds reversibly inhibited NMDA receptor currents by 12 +/- 6% to 74 +/- 6%. These results demonstrate that equianesthetic concentrations of inhaled anesthetics can differ considerably in the extent to which they inhibit NMDA receptors. Such differences may be useful for defining the role that this receptor plays in producing the in vivo actions of general anesthetics.