Lactate modulates the activity of primary cortical neurons through a receptor-mediated pathway.
Lactate modulates the activity of primary cortical neurons through a receptor-mediated pathway.
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DOI：
10.1371/journal.pone.0071721
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chatton JY
中科院分区：
文献类型：
--
作者：
Bozzo L;Puyal J;Chatton JY
乳酸盐越来越多地被描述为大脑的能量基质。除了这个仍在争论的代谢作用外，乳酸盐可能对脑细胞有其他影响。在这里，我们描述乳酸作为一种神经调质，能够影响皮层神经元的活动。用钙离子成像技术监测小鼠原代神经元的兴奋性。当与葡萄糖一起应用时，乳酸诱导神经元自发钙尖峰频率降低。该效应是可逆的，且具有浓度依赖性（IC 50 ≤ 4.2 mM）。为了测试乳酸盐的作用是否依赖于能量代谢，我们应用了密切相关的底物丙酮酸盐（5 mM）或转换为不同的葡萄糖浓度（0.5或10 mM）。这些条件都不能再现乳酸盐的作用。最近，已经引入了称为HCA 1的乳酸的Gi蛋白偶联受体。为了测试该受体是否与观察到的乳酸盐敏感性有关，我们将细胞与百日咳毒素（PTX）--Gi蛋白的抑制剂--孵育。PTX可防止L-乳酸引起的神经元活性降低。此外，HCA 1受体的特异性激动剂3，5-二羟基苯甲酸模仿乳酸的作用。这项研究表明，乳酸通过受体介导的机制对神经元活动进行负反馈，而不依赖于其细胞内代谢。
Lactate is increasingly described as an energy substrate of the brain. Beside this still debated metabolic role, lactate may have other effects on brain cells. Here, we describe lactate as a neuromodulator, able to influence the activity of cortical neurons. Neuronal excitability of mouse primary neurons was monitored by calcium imaging. When applied in conjunction with glucose, lactate induced a decrease in the spontaneous calcium spiking frequency of neurons. The effect was reversible and concentration dependent (IC50 ∼4.2 mM). To test whether lactate effects are dependent on energy metabolism, we applied the closely related substrate pyruvate (5 mM) or switched to different glucose concentrations (0.5 or 10 mM). None of these conditions reproduced the effect of lactate. Recently, a Gi protein-coupled receptor for lactate called HCA1 has been introduced. To test if this receptor is implicated in the observed lactate sensitivity, we incubated cells with pertussis toxin (PTX) an inhibitor of Gi-protein. PTX prevented the decrease of neuronal activity by L-lactate. Moreover 3,5-dyhydroxybenzoic acid, a specific agonist of the HCA1 receptor, mimicked the action of lactate. This study indicates that lactate operates a negative feedback on neuronal activity by a receptor-mediated mechanism, independent from its intracellular metabolism.
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DOI：
10.1016/b978-0-12-385952-5.00005-1
发表时间：
2011-01-01
期刊：
PHARMACOLOGY OF G PROTEIN COUPLED RECEPTORS
影响因子：
--
作者：
Blad, Clara C.;Ahmed, Kashan;Offermanns, Stefan
通讯作者：
Offermanns, Stefan
影响因子：
4.2
作者：
Alessandri, Beat;Schwandt, Eike;Kempski, Oliver
通讯作者：
Kempski, Oliver
影响因子：
168.9
作者：
MARAN, A;CRANSTON, I;AMIEL, SA
通讯作者：
AMIEL, SA
DOI：
10.1097/00004647-200203000-00004
发表时间：
2002-03-01
影响因子：
6.3
作者：
Abi-Saab, WM;Maggs, DG;Sherwin, RS
通讯作者：
Sherwin, RS
影响因子：
7.7
作者：
González JA;Jensen LT;Fugger L;Burdakov D
通讯作者：
Burdakov D