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Potential mechanism of GABA secretion in response to the activation of GluK1-containing kainate receptors
Neuroscience Research ( IF 2.9 ) Pub Date : 2021-03-27 , DOI: 10.1016/j.neures.2021.03.009
S A Maiorov 1 , V P Zinchenko 1 , S G Gaidin 1 , A M Kosenkov 1
Affiliation  

Hippocampal GABAergic neurons are subdivided into more than 20 subtypes that are distinguished by features and functions. We have previously described the subpopulation of GABAergic neurons, which can be identified in hippocampal cell culture by the calcium response to the application of domoic acid (DoA), an agonist of kainate receptors (KARs). Here, we investigate the features of DoA-sensitive neurons and their GABA release mechanism in response to KARs activation. We demonstrate that DoA-sensitive GABAergic neurons express GluK1-containing KARs because ATPA, a selective agonist of GluK1-containing receptors, induces the calcium response exclusively in these GABAergic neurons. Our experiments also show that NASPM, previously considered a selective antagonist of calcium-permeable AMPARs, blocks calcium-permeable KARs. We established using NASPM that GluK1-containing receptors of the studied population of GABAergic neurons are calcium-permeable, and their activation is required for GABA release, at least in particular synapses. Notably, GABA release occurs even in the presence of tetrodotoxin, indicating that propagation of the depolarizing stimulus is not required for GABA release in this case. Thus, our data demonstrate that the activation of GluK1-containing calcium-permeable KARs mediates the GABA release by the studied subpopulation of GABAergic neurons.



中文翻译:

GABA 分泌响应含有 GluK1 的红藻氨酸受体激活的潜在机制

海马 GABA 能神经元细分为 20 多个亚型,这些亚型通过特征和功能进行区分。我们之前已经描述了 GABA 能神经元的亚群,它可以在海马细胞培养物中通过钙对应用软骨藻酸 (DoA),红藻氨酸受体 (KARs) 的激动剂的反应来识别。在这里,我们研究了 DoA 敏感神经元的特征及其响应 KAR 激活的 GABA 释放机制。我们证明 DoA 敏感 GABA 能神经元表达含 GluK1 的 KAR,因为ATPA(一种含 GluK1 受体的选择性激动剂)仅在这些 GABA 能神经元中诱导钙反应。我们的实验还表明,以前被认为是钙渗透性 AMPAR 的选择性拮抗剂的 NASPM 阻断了钙渗透性 KAR。我们使用 NASPM 确定,所研究的 GABA 能神经元群的含 GluK1 受体是钙可渗透的,并且它们的激活是 GABA 释放所必需的,至少在突触中如此。值得注意的是,即使在河豚毒素存在的情况下也会发生 GABA 释放,这表明在这种情况下,GABA 释放不需要去极化刺激的传播。因此,我们的数据表明,含有 GluK1 的钙渗透性 KAR 的激活介导了所研究的 GABA 能神经元亚群的 GABA 释放。表明在这种情况下 GABA 释放不需要去极化刺激的传播。因此,我们的数据表明,含有 GluK1 的钙渗透性 KAR 的激活介导了所研究的 GABA 能神经元亚群的 GABA 释放。表明在这种情况下 GABA 释放不需要去极化刺激的传播。因此,我们的数据表明,含有 GluK1 的钙渗透性 KAR 的激活介导了所研究的 GABA 能神经元亚群的 GABA 释放。

更新日期:2021-03-27
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