Electrophysiological properties and subunit composition of GABAA receptors in patients with gelastic seizures and hypothalamic hamartoma.
Electrophysiological properties and subunit composition of GABAA receptors in patients with gelastic seizures and hypothalamic hamartoma.
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痉挛性癫痫发作和下丘脑错构瘤患者 GABAA 受体的电生理特性和亚基组成。
DOI：
10.1152/jn.00165.2007
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发表时间：
2007
影响因子：
2.5
通讯作者：
Kerrigan,JohnF
中科院分区：
文献类型：
--
作者：
Wu,Jie;Chang,Yongchang;Li,Guohui;Xue,Fenqin;DeChon,Jamie;Ellsworth,Kevin;Liu,Qiang;Yang,Kechun;Bahadroani,Nasim;Zheng,Chao;Zhang,Jianliang;Rekate,Harold;Rho,JongM;Kerrigan,JohnF
GABA A受体结构和/或功能的缺失与人类和动物中各种形式的癫痫有关。这是否适用于痉挛性发作和下丘脑错构瘤（HH）患者尚不清楚。在这项研究中，我们的特点是急性分离的单个神经元手术切除HH组织使用膜片钳，免疫细胞化学和RT-PCR技术的药理学特性和天然亚基组成的GABAA受体。结果表明：（1）GABA在-60 mV的保持电位下诱导一个内向电流（IGABA），（2）IGABA可被GABA A受体激动剂蝇蕈醇模拟，并被GABA A受体拮抗剂荷包牡丹碱阻断，表明IGABA主要通过GABA A受体介导，（3）由IGABA浓度-反应曲线推导出的EC_（50）和Hill系数分别为6.8 μM和1.9; 4）电流-电压曲线在接近于零的反转电位处呈线性，5）IGABA对锌和地西泮的敏感性较低，对戊巴比妥和孕烷醇酮的敏感性较高。此外，我们用正常人下丘脑组织微移植异种卵母细胞，证实GABA A受体的功能特性与小的分离HH神经元中所见的相似。最后，从正常对照人下丘脑组织中获得的GABA A受体亚单位的表达谱与从手术切除的人HH组织中获得的表达谱相同。总之，我们的数据表明，小HH神经元上的GABA A受体表现出正常的药物敏感性和亚基组成。这些发现与更广泛地理解人类HH组织中的抑制性神经传递相关。
Abnormalities in GABAAreceptor structure and/or function have been associated with various forms of epilepsy in both humans and animals. Whether this is true for patients with gelastic seizures and hypothalamic hamartoma (HH) is unknown. In this study, we characterized the pharmacological properties and native subunit composition of GABAAreceptors on acutely dissociated single neurons from surgically resected HH tissues using patch-clamp, immunocytochemical, and RT-PCR techniques. We found that1) GABA induced an inward current (IGABA) at a holding potential of −60 mV;2)IGABAwas mimicked by the GABAAreceptor agonist muscimol and blocked by the GABAAreceptor antagonist bicuculline, suggesting thatIGABAwas mediated principally through the GABAAreceptor;3) the EC50and Hill coefficient derived from theIGABAconcentration-response curve were 6.8 μM and 1.9, respectively;4) the current-voltage curve was linear at a reversal potential close to zero; and5)IGABAexhibited low sensitivity to zinc and diazepam but higher sensitivity to pentobarbital and pregnanolone. Additionally, usingXenopusoocytes microtransplanted with normal human hypothalamic tissue, we confirmed that the functional properties of GABAAreceptors were similar to those seen in small isolated HH neurons. Finally, the expression profile of GABAAreceptor subunits obtained from normal control human hypothalamic tissue was identical to that from surgically resected human HH tissue. Taken together, our data indicate that GABAAreceptors on small HH neurons exhibit normal pharmacosensitivity and subunit composition. These findings bear relevance to a broader understanding of inhibitory neurotransmission in human HH tissue.