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[海人酸受体激活增强海马CA1区中间神经元的紧张性和相位性γ-氨基丁酸能抑制作用]

[Kainate receptor activation enhances both tonic and phasic GABA-ergic inhibition in CA1 hippocampal interneurons].

作者信息

Sem'ianov A V

机构信息

Institute of Neurology, University College London, London, Great Britain.

出版信息

Zh Vyssh Nerv Deiat Im I P Pavlova. 2003 Mar-Apr;53(2):191-8.

Abstract

Kainate receptor agonists are powerful convulsants and excitotoxins. It has been a lot of controversy around functions of these receptors in the brain. It is shown in this article that kainate enhances evoked GABAergic IPSC (phasic currents) in CA1 interneurons in concentration-dependent manner. The phenomenon is likely to be due to kainate-mediated lowering of the threshold for action potential generation in interneuron axons and increased number of terminals responding to the same stimulus strength. Kainate application also induced an enhancement in tonic GABAergic conductance. This phenomenon can be attributed to massive extracellular GABA accumulation caused by interneuron firing in the presence of kainate. Extracellular GABA also shunts synaptic currents by activating tonic conductance as well as desensitizing synaptic GABAA receptors. Thus, the enhancement of the evoked IPSCs by 1 microM kainate was complicated by early and transient decrease. The kainate receptor-mediated enhancement of GABAergic tonic and phasic signalling to interneurons can contribute to the depression of GABAergic transmission to pyramidal neurons. The consequence of this phenomenon may play a major role in the epileptogenic action of this agent.

摘要

海人酸受体激动剂是强效惊厥剂和兴奋性毒素。围绕这些受体在大脑中的功能一直存在很多争议。本文表明,海人酸以浓度依赖的方式增强CA1中间神经元中诱发的GABA能抑制性突触后电流(时相电流)。这种现象可能是由于海人酸介导的中间神经元轴突动作电位产生阈值降低以及对相同刺激强度做出反应的终末数量增加。应用海人酸还会诱导持续性GABA能电导增强。这种现象可归因于在存在海人酸的情况下中间神经元放电导致的大量细胞外GABA积累。细胞外GABA还通过激活持续性电导以及使突触GABAA受体脱敏来分流突触电流。因此,1微摩尔海人酸引起的诱发抑制性突触后电流增强因早期短暂降低而变得复杂。海人酸受体介导的向中间神经元的GABA能持续性和时相性信号增强可能导致向锥体神经元的GABA能传递受到抑制。这种现象的后果可能在该药物的致痫作用中起主要作用。

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