Tonic activation of NMDA receptors by ambient glutamate of non-synaptic origin in the rat hippocampus
Tonic activation of NMDA receptors by ambient glutamate of non-synaptic origin in the rat hippocampus
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DOI：
10.1113/jphysiol.2006.123570
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发表时间：
2007-04-15
影响因子：
5.5
通讯作者：
Audinat, Etienne
中科院分区：
文献类型：
--
作者：
Le Meur, Karim;Galante, Micaela;Audinat, Etienne
在CNS的几种神经元类型中，谷氨酸和GABA受体介导持续电流，其反映了细胞外空间中低浓度递质的存在。在这里，我们进一步的特点，紧张电流介导的环境谷氨酸在大鼠海马脑片。在CA 1和下托区域的几乎所有锥体细胞中检测到具有电压依赖性和NMDA受体（NMDARs）药理学的小幅度强直电流（+40 mV时为53.99 +/- 6.48 pA）。旨在增加D-丝氨酸或甘氨酸细胞外浓度的操作未能改变该电流，这表明介导强直电流的NMDAR的甘氨酸结合位点饱和。与此相反，非转运抑制剂的谷氨酸转运体增加了这种紧张电流的幅度，表明细胞外浓度的谷氨酸主要调节其幅度。AMPA/红藻氨酸受体和代谢型谷氨酸受体都没有对锥体神经元的这种紧张性兴奋做出显着贡献。然而，在谷氨酸转运体抑制剂的存在下，一个显着的比例的紧张性电导介导的AMPA受体。强直电流是不受影响的，当抑制囊泡释放的神经元递质，但增加后，在神经胶质细胞中的谷氨酰胺转换酶的抑制。这些观察结果表明，环境谷氨酸主要是神经胶质来源。最后，使用依赖性拮抗剂MK 801的实验表明，NMDAR介导的紧张性电导可能是突触外NMDAR。
In several neuronal types of the CNS, glutamate and GABA receptors mediate a persistent current which reflects the presence of a low concentration of transmitters in the extracellular space. Here, we further characterize the tonic current mediated by ambient glutamate in rat hippocampal slices. A tonic current of small amplitude (53.99 +/- 6.48 pA at +40 mV) with the voltage dependency and the pharmacology of NMDA receptors (NMDARs) was detected in virtually all pyramidal cells of the CA1 and subiculum areas. Manipulations aiming at increasing D-serine or glycine extracellular concentrations failed to modify this current indicating that the glycine binding sites of the NMDARs mediating the tonic current were saturated. In contrast, non-transportable inhibitors of glutamate transporters increased the amplitude of this tonic current, indicating that the extracellular concentration of glutamate primarily regulates its magnitude. Neither AMPA/kainate receptors nor metabotropic glutamate receptors contributed significantly to this tonic excitation of pyramidal neurons. In the presence of glutamate transporter inhibitors, however, a significant proportion of the tonic conductance was mediated by AMPA receptors. The tonic current was unaffected when inhibiting vesicular release of transmitters from neurons but was increased upon inhibition of the enzyme converting glutamate in glutamine in glial cells. These observations indicate that ambient glutamate is mainly of glial origin. Finally, experiments with the use-dependent antagonist MK801 indicated that NMDARs mediating the tonic conductance are probably extra-synaptic NMDARs.