Group I metabotropic glutamate receptors activate a calcium-sensitive transient receptor potential-like conductance in rat hippocampus
Group I metabotropic glutamate receptors activate a calcium-sensitive transient receptor potential-like conductance in rat hippocampus
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DOI：
10.1113/jphysiol.2002.032961
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发表时间：
2003-02-01
影响因子：
5.5
通讯作者：
Gerber, U
中科院分区：
文献类型：
--
作者：
Gee, CE;Benquet, P;Gerber, U
在来自器官型切片培养物的CA 3锥体神经元中，G（q）偶联的I组代谢型谷氨酸受体（mGluRs）的激活诱导增强兴奋性的非选择性阳离子电导。我们发现，这种响应与由瞬时受体电位（TRP）离子通道家族介导的电导具有多个特性，包括La 3+、2-氨基乙氧基二苯硼烷（2APB）、顺式-N-（2-苯基环戊基）氮杂环十三碳-1-烯-2-胺（MDL 12，330 A）的抑制作用以及双重整流电流-电压关系。mGluR 1和mGluR 5的刺激以协同的方式会聚以激活TRP样电导，并且单独激活任一亚型仅产生正常反应的一小部分。阳离子电流的激活需要升高的细胞内Ca 2+。螯合细胞内Ca 2+或阻断Ca 2+通过电压门控Ca 2+通道进入减弱了对mGluRs激活的反应。相反，提高细胞内Ca 2+增强mGluR激活TRP样电导。在对照条件下，使用细胞内GDP β S阻断G蛋白活化，使用或不使用N-（2，6-二甲基苯基氨基甲酰基甲基）三乙基氯化铵（QX-314）阻止mGluR介导的TRP样电导的活化。然而，G蛋白阻断后，mGluRs 1和/或5与TRP样电导之间的偶联通过增加细胞内Ca 2+被拯救。这表明G蛋白非依赖性信号通路也被I组mGluRs激活。这样的途径可能代表了一种替代的转导机制，以维持代谢型反应的条件下，G蛋白是功能性解偶联从其同源受体。
In CA3 pyramidal neurons from organotypic slice cultures, activation of G(q)-coupled group I metabotropic glutamate receptors (mGluRs) induces a non-selective cationic conductance that enhances excitability. We have found that this response shares several properties with conductances that are mediated by the transient receptor potential (TRP) family of ion channels, including inhibition by La3+, 2-aminoethoxydiphenylborane (2APB), cis-N- (2-phenylcyclopentyl)azacyclotridec-1-en-2-amine (MDL 12,330A) and a doubly rectifying current-voltage relationship. Stimulation of mGluR1 and mGIuR5 converged to activate the TRP-like conductance in a synergistic manner, and activation of either subtype alone produced only a fraction of the normal response. Activation of the cationic current required elevated intracellular Ca2+. Chelating intracellular Ca2+ or blocking Ca2+ entry through voltage-gated Ca2+ channels attenuated responses to the activation of mGluRs. Conversely, raising intracellular Ca2+ potentiated mGluR activation of the TRP-like conductance. Under control conditions, blocking G protein activation using intracellular GDPbetaS with or without N-(2,6-dimethylphenylcarbamoylmethyl) triethylammoniurn chloride (QX-314) prevented mGluR-mediated activation of the TRP-like conductance. Following G protein blockade, however, the coupling between mGluRs 1 and/or 5 and the TRP-like conductance was rescued by increasing intracellular Ca2+. This suggests that a G protein-independent signalling pathway is also activated by group I mGluRs. Such a pathway may represent an alternative transduction mechanism to maintain metabotropic responses under conditions where G proteins are functionally uncoupled from their cognate receptors.