Norepinephrine is one of the key neurotransmitters in the hippocampus, but its role in the functioning of the neuroglial networks remains unclear. Here we show that norepinephrine suppresses NH4 Cl-induced oscillations of the intracellular Ca2+ concentration ([Ca2+ ]i ) in hippocampal neurons. We found that the inhibitory effect of norepinephrine against ammonium-induced [Ca2+ ]i oscillations is mediated by activation of alpha-2 adrenergic receptors. Furthermore, UK 14,304, an agonist of alpha-2 adrenergic receptors, evokes a biphasic [Ca2+ ]i elevation in a minor population of astrocytes. This elevation consists of an initial fast, peak-shaped [Ca2+ ]i rise, mediated by Giβγ subunit and subsequent PLC-induced mobilization of Ca2+ from internal stores, and a plateau phase, mediated by a Ca2+ influx from the extracellular medium through store-operated and TRPC3 channels. We show the correlation between the Ca2+ response in astrocytes and suppression of [Ca2+ ]i oscillations in neurons. The inhibitory effect of UK 14,304 is abolished in the presence of gallein, an inhibitor of Gβγ -signaling. In turn, application of the agonist in the presence of the PLC inhibitor decreases the frequency and amplitude of [Ca2+ ]i oscillations in neurons but does not suppress them. The same effect is observed in the presence of bicuculline, a GABA(A) receptor antagonist. We demonstrate that UK 14,304 application increases the frequency and amplitude of slow outward chloride currents in neurons, indicating the release of GABA by astrocytes. Thus, our findings indicate that the activation of astrocytic alpha-2 adrenergic receptors stimulates GABA release from astrocytes via Giβγ subunit-associated signaling pathway, contributing to the suppression of neuronal activity.

中文翻译：

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α-2 肾上腺素能受体的激活刺激星形胶质细胞释放 GABA。

去甲肾上腺素是海马体中的关键神经递质之一，但其在神经胶质网络功能中的作用仍不清楚。在这里，我们显示去甲肾上腺素抑制海马神经元中 NH4 Cl 诱导的细胞内 Ca2+ 浓度 ([Ca2+ ]i ) 的振荡。我们发现去甲肾上腺素对铵诱导的 [Ca2+]i 振荡的抑制作用是由 α-2 肾上腺素能受体的激活介导的。此外，UK 14,304，一种 α-2 肾上腺素能受体激动剂，在少数星形胶质细胞中引起双相 [Ca2+]i 升高。这种升高包括由 Giβγ 亚基介导的初始快速、峰形 [Ca2+]i 升高和随后 PLC 诱导的 Ca2+ 从内部储存中的动员，以及一个平台期，由细胞外介质通过存储操作和 TRPC3 通道的 Ca2+ 流入介导。我们展示了星形胶质细胞中 Ca2+ 反应与神经元中 [Ca2+]i 振荡抑制之间的相关性。UK 14,304 的抑制作用在gallein（一种 Gβγ 信号传导抑制剂）的存在下被消除。反过来，在存在 PLC 抑制剂的情况下应用激动剂会降低神经元中 [Ca2+]i 振荡的频率和幅度，但不会抑制它们。在荷包牡丹碱（一种 GABA(A) 受体拮抗剂）存在的情况下观察到相同的效果。我们证明 UK 14,304 应用增加了神经元中缓慢向外氯电流的频率和幅度，表明星形胶质细胞释放 GABA。因此，