Discrimination of post- and presynaptic GABAB receptor-mediated responses by tetrahydroaminoacridine in area CA3 of the rat hippocampus.
Discrimination of post- and presynaptic GABAB receptor-mediated responses by tetrahydroaminoacridine in area CA3 of the rat hippocampus.
复制标题
大鼠海马 CA3 区四氢氨基吖啶对突触后和突触前 GABAB 受体介导的反应的区分。
DOI：
10.1152/jn.1993.69.2.630
复制
发表时间：
1993
影响因子：
2.5
通讯作者：
Wilson,WA
中科院分区：
文献类型：
--
作者：
Lambert,NA;Wilson,WA
1.在大鼠海马脑片CA 3区用全细胞电压钳记录技术研究了钾通道阻断剂9-氨基-1，2，3，4-四氢吖啶（THA）对巴氯芬和γ-氨基丁酸（GABA）作用于突触后和突触前GABAB受体的影响。2.在葡萄糖酸钾和三磷酸鸟苷（GTP）灌流的神经元中研究了THA对突触后GABAB受体介导的反应的影响。在-70 mV的保持电位下，GABAB受体激动剂（+/-）-巴氯芬（30 μ M）诱导外向电流并增加膜电导。在兴奋性氨基酸受体拮抗剂6，7-二硝基喹喔啉-2，3-二酮（DNQX）和（+/-）-2-氨基-5-磷酸戊酸（APV）存在下，刺激纹状体或近端辐射层诱发GABAA受体介导的快单突触抑制性突触后电流（IPSC）和GABAB受体介导的晚单突触抑制性IPSC。THA（0.3 mM）阻断了细菌诱导的电流和电导增加以及GABAB受体介导的IPSC。3. THA对突触前GABAB受体介导的反应的影响在用Cs+和利多卡因N-乙基溴（QX-314）内部灌注的神经元中进行了研究，其阻断突触后GABAB受体介导的反应。在DNQX和APV存在下的刺激诱发GABAA受体介导的IPSC;当成对的刺激相隔200 ms时，第二IPSC被抑制。巴氯芬可逆性抑制IPSC，IPSC和部分闭塞的双脉冲抑制。GABAB受体拮抗剂CGP 35348（0.5-1.0 mM）逆转了Bacterium诱导的IPSC抑制，并部分阻断了成对脉冲抑制。Bacterium诱导的IPSC的双脉冲抑制不受THA（0.3 mM）的影响。4.巴氯芬可逆地降低自发单突触IPSC（sIPSC）的振幅和频率。巴氯芬对sIPSCs的抑制作用在THA中没有变化。5.这些结果表明，THA阻断巴氯芬和GABA在突触后而非突触前GABAB受体的作用。我们的结论是，突触后和突触前GABAB受体在大鼠海马CA 3区耦合到不同的效应机制;突触后GABAB受体激活THA敏感的K+通道，突触前GABAB受体通过THA不敏感的机制减少神经递质的释放。
1. The effects of the K+ channel blocker 9-amino-1,2,3,4-tetrahydroacridine (THA) on the actions of baclofen and gamma-aminobutyric acid (GABA) at post- and presynaptic GABAB receptors were studied with whole-cell voltage-clamp recording in area CA3 of rat hippocampal slices. 2. The effect of THA on postsynaptic GABAB receptor-mediated responses was studied in neurons perfused internally with potassium gluconate and guanosine triphosphate (GTP). At a holding potential of -70 mV, the GABAB receptor agonist (+/-)-baclofen (30 microM) induced an outward current and increased membrane conductance. In the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and (+/-)-2-amino-5-phosphonovalerate (APV), stimulation in stratum pyramidale or proximal stratum radiatum evoked GABAA receptor-mediated, fast monosynaptic inhibitory postsynaptic currents (IPSCs) and GABAB receptor-mediated, late monosynaptic IPSCs. THA (0.3 mM) blocked the baclofen-induced current and conductance increase and GABAB receptor-mediated IPSCs. 3. The effect of THA on presynaptic GABAB receptor-mediated responses was studied in neurons perfused internally with Cs+ and lidocaine N-ethyl bromide (QX-314), which blocked post-synaptic GABAB receptor-mediated responses. Stimulation in the presence of DNQX and APV evoked GABAA receptor-mediated IPSCs; when pairs of stimuli were delivered 200 ms apart the second IPSC was depressed. Baclofen reversibly depressed IPSCs, and partially occluded paired-pulse depression of IPSCs. The GABAB receptor antagonist CGP 35348 (0.5-1.0 mM) reversed baclofen-induced depression of IPSCs and partially blocked paired-pulse depression. Baclofen-induced and paired-pulse depression of IPSCs were not by affected by THA (0.3 mM). 4. Baclofen reversibly decreased the amplitude and frequency of spontaneous monosynaptic IPSCs (sIPSCs). Depression of sIPSCs by baclofen was unchanged by THA. 5. These results indicate that THA blocks the actions of baclofen and GABA at post- but not presynaptic GABAB receptors. We conclude that post- and presynaptic GABAB receptors in area CA3 of the rat hippocampus couple to different effector mechanisms; postsynaptic GABAB receptors activate THA-sensitive K+ channels, and presynaptic GABAB receptors decrease neurotransmitter release through a THA-insensitive mechanism.