Both mGluR1 and mGluR5 mediate Ca2+ release and inward currents in hippocampal CA1 pyramidal neurons
Both mGluR1 and mGluR5 mediate Ca2+ release and inward currents in hippocampal CA1 pyramidal neurons
复制标题
DOI：
10.1016/j.neuropharm.2004.02.002
复制
发表时间：
2004-06
影响因子：
4.7
通讯作者：
M. Rae;A. Irving
中科院分区：
文献类型：
--
作者：
M. Rae;A. Irving
通过结合全细胞电压钳记录和 Ca2+ 成像，我们进一步研究了大鼠海马 CA1 锥体神经元中 I 类代谢型 L-谷氨酸受体 (mGluR) 介导的反应的特征和药理学。选择性 I 组 mGluR 激动剂 (RS)-3,5-二羟基苯基甘氨酸 (DHPG) 会引起神经元胞体和顶端树突内细胞内 Ca2+ 水平 ([Ca2+]i) 的短暂增加，以及相对较长持续的内向电流 (IDHPG)。两种类型的响应均通过去极化（−30 mV）得到增强，并且该条件用于它们的表征。与 IDHPG 相比，DHPG 诱导的 [Ca2+] 鸢尾花对 Ca2+ 稳态的操作更为敏感，例如使用 Ca2+ 储存消耗剂、环匹阿尼酸 (50–100 μM)、快速 Ca2+ 缓冲液、BAPTA（细胞内；20–40 mM）和无 Ca2+/EGTA (1 mM) 浴液，这表明这些反应主要是部分，由不同的过程介导。选择性 mGluR1 和 mGluR5 拮抗剂 (S)-(+)-α-氨基-α-甲基苯乙酸 (LY367385；100 μM) 和 2-甲基-6-(苯乙炔基)-吡啶 (MPEP；10 μM) 分别显着抑制 IDHPG 和 DHPG 引起的 [Ca2+]i 增加。 Ca2+ 反应超过 50%，表明 mGluR1 和 mGluR5 之间存在协同相互作用。这项研究表明，在 CA1 锥体神经元中，I 组 mGluR 介导的内向电流和细胞内储存的 Ca2+ 释放在去极化条件下增强，并且 mGluR1 和 mGluR5 都对这些现象有贡献。
Using combined whole-cell voltage-clamp recording and Ca2+imaging we have investigated further the characteristics and pharmacology of group I metabotropic l-glutamate receptor (mGluR)-mediated responses in CA1 pyramidal neurons of the rat hippocampus. The selective group I mGluR agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG), evoked a transient increase in intracellular Ca2+levels ([Ca2+]i), within neuronal somas and apical dendrites, together with a relatively long lasting inward current (IDHPG). Both types of response were enhanced by depolarisation (−30 mV), and this condition was used for their characterisation. The DHPG-induced [Ca2+]irise was much more sensitive to manipulations of Ca2+homeostasis, such as using the Ca2+store depleting agent, cyclopiazonic acid (50–100 μM), the fast Ca2+buffer, BAPTA (intracellular; 20–40 mM) and Ca2+-free/EGTA (1 mM) bath solution, than IDHPG, suggesting that these responses are, in the main part, mediated by distinct processes. The selective mGluR1 and mGluR5 antagonists, (S)-(+)-α-amino-a-methylbenzeneacetic acid (LY367385; 100 μM) and 2-methyl-6-(phenylethynyl)-pyridine (MPEP;10 μM), respectively, markedly inhibited both IDHPGand the DHPG-evoked increase in [Ca2+]i.Moreover, these antagonists inhibited the Ca2+response by more than 50% suggesting a synergistic interaction between mGluR1 and mGluR5. This study demonstrates that in CA1 pyramidal neurons group I mGluR-mediated inward currents and Ca2+release from intracellular stores are enhanced under depolarising conditions and that mGluR1 and mGluR5 both contribute to these phenomena.