Genetic reduction of GABAA receptor γ2 subunit expression potentiates the immobilizing action of isoflurane
Genetic reduction of GABAA receptor γ2 subunit expression potentiates the immobilizing action of isoflurane
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DOI：
10.1016/j.neulet.2010.01.031
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发表时间：
2010-03-12
影响因子：
2.5
通讯作者：
Hirata, Masato
中科院分区：
文献类型：
--
作者：
Seo, Kenji;Seino, Hiroyuki;Hirata, Masato
抑制性γ -氨基丁酸亚型A（GABA(A)）受体功能的增强参与了麻醉作用的机制。本研究研究了挥发性麻醉药异氟醚在双敲除（DKO）磷脂酶c相关失活蛋白(PRIP)-1和-2小鼠体内的固定化作用。这两种蛋白在神经元细胞表面含有γ - 2亚基的GABA(A)受体的表达中起重要作用。GABA(A)受体亚基免疫组化显示DKO小鼠脊髓中γ - 2亚基的表达减少。免疫组织化学也显示α 1和β 3亚基上调，尽管野生型和DKO小鼠对β 2亚基的免疫反应性没有明显差异。采用尾钳法评价异氟醚的麻醉/固定作用，DKO小鼠的最小肺泡浓度（MAC）明显低于野生型对照（1.07 +/- 0.01% vs 1.36 +/- 0.04% atm），表明DKO小鼠对异氟醚的敏感性增加。这些免疫组织化学和药理学研究结果表明，GABA(A)受体γ - 2亚基的表达减少会影响脊髓GABA(A)受体的组成和功能，并增强异氟烷的固定作用。2010爱思唯尔爱尔兰有限公司版权所有。
Potentiation of inhibitory gamma-aminobutyric acid subtype A (GABA(A)) receptor function is involved in the mechanisms of anesthetic action. The present study examined the immobilizing action of the volatile anesthetic isoflurane in mice with double knockout (DKO) of phospholipase C-related inactive protein (PRIP)-1 and -2. Both of these proteins play important roles in the expression of GABA(A) receptors containing the gamma 2 subunit on the neuronal cell surface. Immunohistochemistry for GABA(A) receptor subunits demonstrated reduced expression of gamma 2 subunits in the spinal cord of the DKO mice. Immunohistochemistry also revealed up-regulation of the alpha 1 and beta 3 subunits even though there were no apparent differences in the immunoreactivities for the beta 2 subunits between wild-type and DKO mice. The tail-clamp method was used to evaluate the anesthetic/immobilizing effect of isoflurane and the minimum alveolar concentration (MAC) was significantly lower in DKO mice compared with wild-type controls (1.07 +/- 0.01% versus 1.36 +/- 0.04% atm), indicating an increased sensitivity to isoflurane in DKO mice. These immunohistochemical and pharmacological findings suggest that reduced expression of the GABA(A) receptor gamma 2 subunit affects the composition and function of spinal GABA(A) receptors and potentiates the immobilizing action of isoflurane. (C) 2010 Elsevier Ireland Ltd. All rights reserved.