Le Meur Karim, Galante Micaela, Angulo María Cecilia, Audinat Etienne
Inserm U603, Université Paris Descartes, 45 rue des Saints Pères, 75006 Paris, France.
J Physiol. 2007 Apr 15;580(Pt. 2):373-83. doi: 10.1113/jphysiol.2006.123570. Epub 2006 Dec 21.
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.
在中枢神经系统的几种神经元类型中，谷氨酸和γ-氨基丁酸（GABA）受体介导一种持续性电流，该电流反映了细胞外空间中低浓度递质的存在。在此，我们进一步对大鼠海马切片中由细胞外谷氨酸介导的强直电流进行了表征。在CA1区和下托区几乎所有的锥体细胞中，检测到了一种小幅度的强直电流（在+40 mV时为53.99±6.48 pA），其具有NMDA受体（NMDARs）的电压依赖性和药理学特性。旨在提高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NMDARs的甘氨酸结合位点已饱和。相反，谷氨酸转运体的非转运性抑制剂增加了该强直电流的幅度，表明谷氨酸的细胞外浓度主要调节其大小。AMPA/海人藻酸受体和代谢型谷氨酸受体对锥体细胞的这种强直兴奋均无显著贡献。然而，在存在谷氨酸转运体抑制剂的情况下，很大一部分强直电导是由AMPA受体介导的。抑制神经元递质的囊泡释放时，强直电流不受影响，但抑制胶质细胞中谷氨酸转化为谷氨酰胺的酶时，强直电流增加。这些观察结果表明，细胞外谷氨酸主要来源于胶质细胞。最后，使用依赖性拮抗剂MK801的实验表明，介导强直电导的NMDARs可能是突触外NMDARs。
