Jahr C E, Stevens C F
Nature. 1987;325(6104):522-5. doi: 10.1038/325522a0.
There is considerable evidence that glutamate is the principal neurotransmitter that mediates fast excitatory synaptic transmission in the vertebrate central nervous system. This single transmitter seems to activate two or three distinct types of receptors, defined by their affinities for three selective structural analogues of glutamate, NMDA (N-methyl-D-aspartate), quisqualate and kainate. All these agonists increase membrane permeability to monovalent cations, but NMDA also activates a conductance that permits significant calcium influx and is blocked in a voltage-dependent manner by extracellular magnesium. Fast synaptic excitation seems to be mediated mainly by kainate/quisqualate receptors, although NMDA receptors are sometimes activated. We have investigated the properties of these conductances using single-channel recording in primary cultures of hippocampal neurons, because the hippocampus contains all subtypes of glutamate receptors and because long-term potentiation of synaptic transmission occurs in this structure. We find that four or more distinct single-channel currents are evoked by applying glutamate to each outside-out membrane patch. These conductances vary in their ionic permeability and in the agonist most effective in causing them to open. Clear transitions between all the conductance levels are observed. Our observations are compatible with the model that all the single channel conductances activated by glutamate reflect the operation of one or two complex molecular entities.
有大量证据表明，谷氨酸是脊椎动物中枢神经系统中介导快速兴奋性突触传递的主要神经递质。这单一的神经递质似乎激活了两种或三种不同类型的受体，这些受体通过它们对谷氨酸的三种选择性结构类似物——N-甲基-D-天冬氨酸（NMDA）、使君子酸和海人酸的亲和力来定义。所有这些激动剂都会增加膜对单价阳离子的通透性，但NMDA还会激活一种允许大量钙离子内流的电导，并且会被细胞外镁以电压依赖的方式阻断。快速突触兴奋似乎主要由海人酸/使君子酸受体介导，尽管NMDA受体有时也会被激活。我们利用海马神经元原代培养中的单通道记录来研究这些电导的特性，因为海马体包含谷氨酸受体的所有亚型，并且因为突触传递的长时程增强发生在这个结构中。我们发现，向每个外翻膜片施加谷氨酸会诱发四种或更多不同的单通道电流。这些电导在离子通透性以及使其开放最有效的激动剂方面存在差异。观察到所有电导水平之间有清晰的转换。我们的观察结果与这样的模型相符，即谷氨酸激活的所有单通道电导反映了一个或两个复杂分子实体的运作。
