Mulle C, Sailer A, Pérez-Otaño I, Dickinson-Anson H, Castillo P E, Bureau I, Maron C, Gage F H, Mann J R, Bettler B, Heinemann S F
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Nature. 1998 Apr 9;392(6676):601-5. doi: 10.1038/33408.
L-glutamate, the neurotransmitter of the majority of excitatory synapses in the brain, acts on three classes of ionotropic receptors: NMDA (N-methyl-D-aspartate), AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) and kainate receptors. Little is known about the physiological role of kainate receptors because in many experimental situations it is not possible to distinguish them from AMPA receptors. Mice with disrupted kainate receptor genes enable the study of the specific role of kainate receptors in synaptic transmission as well as in the neurotoxic effects of kainate. We have now generated mutant mice lacking the kainate-receptor subunit GluR6. The hippocampal neurons in the CA3 region of these mutant mice are much less sensitive to kainate. In addition, a postsynaptic kainate current evoked in CA3 neurons by a train of stimulation of the mossy fibre system is absent in the mutant. We find that GluR6-deficient mice are less susceptible to systemic administration of kainate, as judged by onset of seizures and by the activation of immediate early genes in the hippocampus. Our results indicate that kainate receptors containing the GluR6 subunit are important in synaptic transmission as well as in the epileptogenic effects of kainate.
L-谷氨酸是大脑中大多数兴奋性突触的神经递质，作用于三类离子型受体：NMDA（N-甲基-D-天冬氨酸）、AMPA（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸）和海人藻酸受体。人们对海人藻酸受体的生理作用了解甚少，因为在许多实验情况下，无法将它们与AMPA受体区分开来。海人藻酸受体基因被破坏的小鼠有助于研究海人藻酸受体在突触传递以及海人藻酸神经毒性作用中的特定作用。我们现已培育出缺乏海人藻酸受体亚基GluR6的突变小鼠。这些突变小鼠CA3区的海马神经元对海人藻酸的敏感性要低得多。此外，在突变体中，由苔藓纤维系统的一连串刺激在CA3神经元中诱发的突触后海人藻酸电流缺失。我们发现，根据癫痫发作的起始情况以及海马中即刻早期基因的激活情况判断，GluR6缺陷型小鼠对全身给予海人藻酸的敏感性较低。我们的结果表明，含有GluR6亚基的海人藻酸受体在突触传递以及海人藻酸的致痫作用中都很重要。
