Tonic benzodiazepine-sensitive GABAergic inhibition in cultured rodent cerebellar granule cells
Tonic benzodiazepine-sensitive GABAergic inhibition in cultured rodent cerebellar granule cells
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DOI：
10.1016/s0028-3908(99)00177-x
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发表时间：
2000-01-01
影响因子：
4.7
通讯作者：
Randall, AD
中科院分区：
文献类型：
--
作者：
Leao, RM;Mellor, JR;Randall, AD
最近的研究表明，大鼠小脑切片中的颗粒细胞表现出紧张形式的GABA能抑制。在新生大鼠小脑的突触偶联培养物中研究了类似的组成性GABA能电导的存在。在表现出自发抑制性突触后电流（IPSC）的细胞中，应用GABA（A）受体拮抗剂荷包牡丹碱（10 μ M）消除了IPSC，并使保持电流显著降低。后一种效应使没有表现出IPSC的细胞中缺乏润湿。MT（1 μ M）和Cd ~（2+）（100 μ M）的应用降低了IPSC的频率，也产生了保持电流的变化，这些影响被预先应用荷包牡丹碱消除。在存在TTX的情况下，应用苯二氮卓类（BDZ）氟硝西泮（1 μ M）引起GABA（A）受体活性引起的保持电流分量增加85+/-15%。噪声分析表明，作为GABA能抑制的这种紧张形式基础的GABA（A）受体表现出接近14 pS的平均单通道电导，该值与在这些细胞中观察到的体细胞GABA（A）受体的值相似。因此，像小脑切片中的对应物一样，培养的小脑颗粒细胞表现出背景GABA能电导。这种紧张性电流最可能的来源是从活跃的抑制性突触中溢出的GABA。由于这种电导对苯二氮卓受体激动剂敏感，因此不太可能完全由含有α 6亚单位的GABA（A）受体引起。(C)2000爱思唯尔科技有限公司版权所有。
Recent studies have demonstrated that granule cells in rat cerebellar slices exhibit a tonic form of GABAergic inhibition. The presence of a similar constitutive GABAergic conductance was investigated in synaptically coupled cultures of neonatal rat cerebellum. In cells exhibiting spontaneous inhibitory postsynaptic currents (IPSCs), application of the GABA(A) receptor antagonist bicuculline (10 mu M) eliminated the IPSCs and also produced a significant decrease in holding current. This latter effect wets lacking in cells that did not exhibit IPSCs. Application of mt (1 mu M) and Cd2+ (100 mu M) decreased the IPSC frequency and also produced a change in holding current, these effects were eliminated by the prior application of bicuculline. In thr presence of TTX, application of the benzodiazepine (BDZ) Flunitrazepam (1 mu M) caused a 85+/-15% increase in the component of holding current that arose from GABA(A) receptor activity. Noise analysis indicated that the GABA(A) receptors underlying this tonic form of GABAergic inhibition exhibited a mean single channel conductance close to 14 pS, a value similar to that seen for somatic GABA(A) receptors in these cells. Thus, like their counterparts in cerebellar slices, cerebellar granule cells in culture exhibit a background GABAergic conductance. The most likely source of this tonic current is GABA spilt over from active inhibitory synapses. As this conductance was sensitive to benzodiazepine receptor agonists it is unlikely to arise entirely from GABA(A) receptors containing the alpha 6 subunit. (C) 2000 Elsevier Science Ltd. All rights reserved.