Castillo P E, Malenka R C, Nicoll R A
Department of Cellular and Molecular Pharmacology, University of California at San Francisco, 94143, USA.
Nature. 1997 Jul 10;388(6638):182-6. doi: 10.1038/40645.
Glutamate, the neurotransmitter at most excitatory synapses in the brain, activates a variety of receptor subtypes that can broadly be divided into ionotropic (ligand-gated ion channels) and metabotropic (G-protein-coupled) receptors. Ionotropic receptors mediate fast excitatory synaptic transmission, and based on pharmacological and molecular biological studies are divided into NMDA and non-NMDA subtypes. The non-NMDA receptor group is further divided into AMPA and kainate subtypes. Virtually all fast excitatory postsynaptic currents studied so far in the central nervous system are mediated by the AMPA and NMDA subtypes of receptors. Surprisingly, despite extensive analysis of their structure, biophysical properties and anatomical distribution, a synaptic role for kainate receptors in the brain has not been found. Here we report that repetitive activation of the hippocampal mossy fibre pathway, which is associated with high-affinity kainate binding and many of the kainate receptor subtypes, generates a slow excitatory synaptic current with all of the properties expected of a kainate receptor. This activity-dependent synaptic current greatly augments the excitatory drive of CA3 pyramidal cells.
谷氨酸是大脑中大多数兴奋性突触的神经递质，它激活多种受体亚型，这些受体大致可分为离子型（配体门控离子通道）和代谢型（G蛋白偶联）受体。离子型受体介导快速兴奋性突触传递，根据药理学和分子生物学研究可分为NMDA和非NMDA亚型。非NMDA受体组进一步分为AMPA和海人藻酸亚型。到目前为止，在中枢神经系统中研究的几乎所有快速兴奋性突触后电流都是由AMPA和NMDA亚型受体介导的。令人惊讶的是，尽管对其结构、生物物理特性和解剖分布进行了广泛分析，但尚未发现海人藻酸受体在大脑中的突触作用。在此我们报告，海马苔藓纤维通路的重复激活与高亲和力海人藻酸结合以及许多海人藻酸受体亚型相关，产生一种具有海人藻酸受体所有预期特性的缓慢兴奋性突触电流。这种活动依赖性突触电流极大地增强了CA3锥体细胞的兴奋性驱动。
