Slow synaptic inhibition mediated by metabotropic glutamate receptor activation of GIRK channels
Slow synaptic inhibition mediated by metabotropic glutamate receptor activation of GIRK channels
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DOI：
10.1152/jn.2000.84.5.2284
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发表时间：
2000-11-01
影响因子：
2.5
通讯作者：
Perkel, DJ
中科院分区：
文献类型：
--
作者：
Dutar, P;Petrozzino, JJ;Perkel, DJ
谷氨酸是脊椎动物中枢神经系统中主要的兴奋性神经递质。离子型谷氨酸受体介导快速兴奋作用，而代谢型谷氨酸受体（mGluRs）介导各种较慢的作用。例如，mGluR可以介导突触前抑制、突触后兴奋或更罕见的突触后抑制。我们以前描述了一种异常缓慢的形式突触后抑制一类投射神经元的鸣禽前脑的歌曲控制核HVC。这些神经元参与发声学习必不可少的回路，表现出持续数秒的抑制性突触后电位（IPSP）。只有一部分这种缓慢的IPSP是由GABAB受体介导的。由于这些细胞被mGluRs激动剂强烈超极化，我们使用脑切片的细胞内记录来研究这种超极化的机制，并确定mGluRs是否有助于缓慢的突触抑制。我们报告说，mGluRs hypertrophy这些HVc神经元通过激活G蛋白偶联，内向整流钾（GIRK）通道。MGluR拮抗剂阻断这种反应和缓慢的突触抑制。因此，谷氨酸可与GABA联合收割机通过激活CNS中的GIRK通道来介导缓慢的突触抑制。
Glutamate is the predominant excitatory neurotransmitter in the vertebrate CNS. Ionotropic glutamate receptors mediate fast excitatory actions whereas metabotropic glutamate receptors (mGluRs) mediate a variety of slower effects. For example, mGluRs can mediate presynaptic inhibition, postsynaptic excitation, or, more rarely, postsynaptic inhibition. We previously described an unusually slow form of postsynaptic inhibition in one class of projection neuron in the song-control nucleus HVc of the songbird forebrain. These neurons, which participate in a circuit that is essential for vocal learning, exhibit an inhibitory postsynaptic potential (IPSP) that lasts several seconds. Only a portion of this slow IPSP is mediated by GABAB receptors. Since these cells are strongly hyperpolarized by agonists of mGluRs, we used intracellular recording from brain slices to investigate the mechanism of this hyperpolarization and to determine whether mGluRs contribute to the slow synaptic inhibition. We report that mGluRs hyperpolarize these HVc neurons by activating G protein-coupled, inwardly-rectifying potassium (GIRK) channels. MGluR antagonists blocked this response and the slow synaptic inhibition. Thus, glutamate can combine with GABA to mediate slow synaptic inhibition by activating GIRK channels in the CNS.