Alterations in Purkinje cell GABAA receptor pharmacology following oxygen and glucose deprivation and cerebral ischemia reveal novel contribution of β1 -subunit-containing receptors.
Alterations in Purkinje cell GABAA receptor pharmacology following oxygen and glucose deprivation and cerebral ischemia reveal novel contribution of β1 -subunit-containing receptors.
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DOI：
10.1111/ejn.12064
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发表时间：
2013-02
期刊：
影响因子：
--
通讯作者：
Herson PS
中科院分区：
文献类型：
--
作者：
Kelley MH;Ortiz J;Shimizu K;Grewal H;Quillinan N;Herson PS
小脑浦肯野细胞（PC）对脑缺血特别敏感，损伤后GABAA受体功能下降被认为有助于PC对缺血诱导的兴奋性毒性的敏感性。在这里，我们研究了GABAA受体的功能特性，在培养的浦肯野细胞从大鼠和小鼠体内缺血缺血后幸免。使用GABAA受体的亚基特异性阳性调节剂，我们观察到氧气和葡萄糖剥夺（OGD）和心脏骤停诱导的脑缺血导致对β2/3亚基偏好化合物依托咪酯的敏感性降低。然而，对异丙酚（一种调节β1-3亚基的β亚基作用化合物）的敏感性不受OGD的影响。α/γ-亚基作用化合物地西泮和唑吡坦也不受OGD的影响。我们对从急性分离的小脑组织中分离的PC进行单细胞逆转录聚合酶链反应，观察到PC表达β1亚基，与以前研究PC中GABAA受体亚基表达的报道相反。在成年小鼠小脑中，通过蛋白质印迹和免疫组织化学在培养的PC中也检测到GABAA受体β1亚基蛋白，并且水平不受缺血的影响。高浓度的loreclezole（30 µm）抑制PC GABA介导的电流，如先前在异源系统中表达的含β1亚基的GABAA受体所证明的。从我们的数据中，我们得出结论，PC表达β1-亚基，并且在OGD后含有β1-亚基的GABAA受体的贡献更大。
Cerebellar Purkinje cells (PCs) are particularly sensitive to cerebral ischemia, and decreased GABAA receptor function following injury is thought to contribute to PC sensitivity to ischemia-induced excitotoxicity. Here we examined the functional properties of the GABAA receptors that are spared following ischemia in cultured Purkinje cells from rat and in vivo ischemia in mouse. Using subunit-specific positive modulators of GABAA receptors, we observed that oxygen and glucose deprivation (OGD) and cardiac arrest-induced cerebral ischemia cause a decrease in sensitivity to the β2/3-subunit-preferring compound, etomidate. However, sensitivity to propofol, a β-subunit-acting compound that modulates β1–3-subunits, was not affected by OGD. The α/γ-subunit-act-ing compounds, diazepam and zolpidem, were also unaffected by OGD. We performed single-cell reverse transcription–polymerase chain reaction on isolated PCs from acutely dissociated cerebellar tissue and observed that PCs expressed the β1-subunit, contrary to previous reports examining GABAA receptor subunit expression in PCs. GABAA receptor β1-subunit protein was also detected in cultured PCs by western blot and by immunohistochemistry in the adult mouse cerebellum and levels remained unaffected by ischemia. High concentrations of loreclezole (30 µm) inhibited PC GABA-mediated currents, as previously demonstrated with β1-subunit-containing GABAA receptors expressed in heterologous systems. From our data we conclude that PCs express the β1-subunit and that there is a greater contribution of β1-subunit-containing GABAA receptors following OGD.
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DOI：
10.1073/pnas.0506653102
发表时间：
2005-10-11
影响因子：
11.1
作者：
Kittler, JT;Chen, GJ;Moss, SJ
通讯作者：
Moss, SJ
影响因子：
3.5
作者：
LI, HL;SIEGEL, RE;SCHWARTZ, RD
通讯作者：
SCHWARTZ, RD
DOI：
10.1073/pnas.94.16.8824
发表时间：
1997-08-05
影响因子：
11.1
作者：
Buhr, A;Sigel, E
通讯作者：
Sigel, E
影响因子：
12.7
作者：
HORN, M;SCHLOTE, W
通讯作者：
SCHLOTE, W
DOI：
10.1073/pnas.94.20.11031
发表时间：
1997-09-30
影响因子：
11.1
作者：
Belelli, D;Lambert, JJ;Whiting, PJ
通讯作者：
Whiting, PJ