Fiorillo C D, Williams J T
Vollum Institute, Oregon Health Sciences University, Portland 97201, USA.
Nature. 1998 Jul 2;394(6688):78-82. doi: 10.1038/27919.
Rapid information transfer within the brain depends on chemical signalling between neurons that is mediated primarily by glutamate and GABA (gamma-aminobutyric acid), acting at ionotropic receptors to cause excitatory or inhibitory postsynaptic potentials (EPSPs or IPSPs), respectively. In addition, synaptically released glutamate acts on metabotropic receptors to excite neurons on a slower timescale through second-messenger cascades, including phosphoinositide hydrolysisl. We now report a unique IPSP mediated by the activation of metabotropic glutamate receptors. In ventral midbrain dopamine neurons, activation of metabotropic glutamate receptors (mGluR1) mobilized calcium from caffeine/ryanodine-sensitive stores and increased an apamin-sensitive potassium conductance. The underlying potassium conductance and dependence on calcium stores set this IPSP apart from the slow IPSPs described so far. The mGluR-induced hyperpolarization was dependent on brief exposure to agonist, because prolonged application of exogenous agonist desensitized the hyperpolarization and caused the more commonly reported depolarization. The rapid rise and brief duration of synaptically released glutamate in the extracellular space can therefore mediate a rapid excitation through activation of ionotropic receptors, followed by inhibition through the mGluR1 receptor. Thus the idea that glutamate is solely an excitatory neurotransmitter must be replaced with a more complex view of its dual function in synaptic transmission.
大脑内的快速信息传递依赖于神经元之间的化学信号传导，这主要由谷氨酸和γ-氨基丁酸（GABA）介导，它们分别作用于离子型受体，引起兴奋性或抑制性突触后电位（EPSP或IPSP）。此外，突触释放的谷氨酸作用于代谢型受体，通过包括磷酸肌醇水解在内的第二信使级联反应，在较慢的时间尺度上兴奋神经元。我们现在报告一种由代谢型谷氨酸受体激活介导的独特IPSP。在腹侧中脑多巴胺能神经元中，代谢型谷氨酸受体（mGluR1）的激活从咖啡因/ryanodine敏感储存库中动员钙，并增加一种蜂毒明肽敏感的钾电导。潜在的钾电导和对钙储存库的依赖性使这种IPSP有别于迄今为止描述的慢IPSP。mGluR诱导的超极化依赖于短暂暴露于激动剂，因为长时间应用外源性激动剂会使超极化脱敏，并导致更常见报道的去极化。因此，细胞外空间中突触释放的谷氨酸的快速上升和短暂持续时间可通过激活离子型受体介导快速兴奋，随后通过mGluR1受体介导抑制。因此，谷氨酸仅仅是一种兴奋性神经递质的观点必须被其在突触传递中双重功能的更复杂观点所取代。
