Effect of Zolpidem on Miniature IPSCs and Occupancy of Postsynaptic GABAA Receptors in Central Synapses
Effect of Zolpidem on Miniature IPSCs and Occupancy of Postsynaptic GABAA Receptors in Central Synapses
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唑吡坦对微型 IPSC 和中枢突触突触后 GABAA 受体占据的影响
DOI：
10.1523/jneurosci.19-02-00578.1999
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
N. Ropert
中科院分区：
文献类型：
--
作者：
D. Perrais;N. Ropert
采用全细胞膜片钳技术记录大鼠脑片视皮层V层锥体神经元中GABA A介导的微型IPSCs（mIPSCs）。在室温下，苯二氮卓类位点激动剂唑吡坦可增强mIPSC的振幅（在10 μm处为对照值的138 ± 26%）和持续时间（163 ± 14%）。mIPSC振幅的增强不是由突触后受体的单通道电导的增加引起的，如通过mIPSC的峰尺度非平稳波动分析所确定的。还研究了唑吡坦对GABA快速、突触样（1 msec持续时间）应用于外向斑的影响。快速GABA应用的EC 50为310 μm。在贴片中，唑吡坦增强了亚饱和GABA应用（100-300 μm）引起的电流幅度，但不增强饱和应用（10 mm）引起的电流幅度。唑吡坦增加mIPSC振幅提供了证据，证明在记录细胞中的微型突触传递期间GABAA受体未饱和。通过比较1 μm唑吡坦在外向斑和mIPSC上诱导的易化作用，我们估计在单个囊泡释放后，突触后GABAA受体观察到的GABA浓度约为300 μm。我们估计在室温和生理温度下受体占有率相似。然而，在35°C下，唑吡坦并没有增强mIPSC的振幅或在贴片上施加亚饱和GABA的振幅，这意味着在这些神经元中，唑吡坦不能用于探测生理温度下受体占据的程度。
GABAA-mediated miniature IPSCs (mIPSCs) were recorded from layer V pyramidal neurons of the visual cortex using whole-cell patch-clamp recording in rat brain slices. At room temperature, the benzodiazepine site agonist zolpidem enhanced both the amplitude (to 138 ± 26% of control value at 10 μm) and the duration (163 ± 14%) of mIPSCs. The enhancement of mIPSC amplitude was not caused by an increase of the single-channel conductance of the postsynaptic receptors, as determined by peak-scaled non-stationary fluctuation analysis of mIPSCs. The effect of zolpidem on fast, synaptic-like (1 msec duration) applications of GABA to outside-out patches was also investigated. The EC50 for fast GABA applications was 310 μm. In patches, zolpidem enhanced the amplitude of currents elicited by subsaturating GABA applications (100–300 μm) but not by saturating applications (10 mm). The increase of mIPSC amplitude by zolpidem provides evidence that the GABAA receptors are not saturated during miniature synaptic transmission in the recorded cells. By comparing the facilitation induced by 1 μm zolpidem on outside-out patches and mIPSCs, we estimated the concentration of GABA seen by the postsynaptic GABAA receptors to be ∼300 μm after single vesicle release. We have estimated a similar degree of receptor occupancy at room and physiological temperature. However, at 35°C, zolpidem did not enhance the amplitude of mIPSCs or of subsaturating GABA applications on patches, implying that, in these neurons, zolpidem cannot be used to probe the degree of receptor occupancy at physiological temperature.
影响因子：
2.5
作者：
Salin, PA;Prince, DA
通讯作者：
Prince, DA
影响因子：
56.9
作者：
CLEMENTS, JD;LESTER, RAJ;WESTBROOK, GL
通讯作者：
WESTBROOK, GL