Potentiation of Glycine-Gated NR1/NR3A NMDA Receptors Relieves Ca-Dependent Outward Rectification.
Potentiation of Glycine-Gated NR1/NR3A NMDA Receptors Relieves Ca-Dependent Outward Rectification.
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DOI：
10.3389/fnmol.2010.00006
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发表时间：
2010
影响因子：
4.8
通讯作者：
Laube B
中科院分区：
文献类型：
--
作者：
Madry C;Betz H;Geiger JR;Laube B
甘氨酸在哺乳动物中枢神经系统中具有多种功能。它通过士的宁敏感的甘氨酸受体（GlyR）抑制突触后神经元，并通过N-甲基-D-天冬氨酸（NMDA）受体的共激活增强神经元兴奋。经典的Ca 2+可渗透NMDA受体由甘氨酸结合NR 1和谷氨酸结合NR 2亚基组成，因此需要谷氨酸和甘氨酸有效激活。相反，由NR 1和甘氨酸结合NR 3A和/或NR 3B亚基组成的重组受体缺乏谷氨酸结合位点，并且可以被甘氨酸单独激活。因此，这些受体也被称为“兴奋性甘氨酸受体”。NR 1甘氨酸结合位点或二价阳离子Zn 2+的拮抗剂的共同应用显著增强这些受体的甘氨酸反应。为了进一步了解这些甘氨酸门控NMDA受体的特性，我们研究了它们的电流-电压（I-V）依赖性。在我们的记录条件下，从表达NR 1/NR 3B和NR 1/NR 3A/NR 3B的卵母细胞记录的甘氨酸电流的全细胞电流-电压关系被发现是线性的。相比之下，NR 1/NR 3A受体表现出强烈的外向整流I-V关系。有趣的是，NR 1拮抗剂，锌+或两者的组合的存在下，电压依赖性内向电流阻滞被取消。进一步的分析表明，Ca 2+（1.8 mM）存在于我们的记录解决方案是负责电压依赖性抑制离子通量通过NR 1/NR 3A受体。由于生理浓度的二价阳离子Mg 2+不影响I-V依赖性，我们的数据表明，根据常规NR 1/NR 2 NMDA受体的Mg 2+阻断，Zn 2+对NR 1/NR 3A受体的电压依赖性Ca 2+阻断的缓解可能对兴奋性甘氨酸能传递的调节是重要的。
Glycine has diverse functions within the mammalian central nervous system. It inhibits postsynaptic neurons via strychnine-sensitive glycine receptors (GlyRs) and enhances neuronal excitation through co-activation of N-methyl-D-aspartate (NMDA) receptors. Classical Ca2+-permeable NMDA receptors are composed of glycine-binding NR1 and glutamate-binding NR2 subunits, and hence require both glutamate and glycine for efficient activation. In contrast, recombinant receptors composed of NR1 and the glycine binding NR3A and/or NR3B subunits lack glutamate binding sites and can be activated by glycine alone. Therefore these receptors are also named “excitatory glycine receptors”. Co-application of antagonists of the NR1 glycine-binding site or of the divalent cation Zn2+ markedly enhances the glycine responses of these receptors. To gain further insight into the properties of these glycine-gated NMDA receptors, we investigated their current-voltage (I–V) dependence. Whole-cell current-voltage relations of glycine currents recorded from NR1/NR3B and NR1/NR3A/NR3B expressing oocytes were found to be linear under our recording conditions. In contrast, NR1/NR3A receptors displayed a strong outwardly rectifying I–V relation. Interestingly, the voltage-dependent inward current block was abolished in the presence of NR1 antagonists, Zn2+ or a combination of both. Further analysis revealed that Ca2+ (1.8 mM) present in our recording solutions was responsible for the voltage-dependent inhibition of ion flux through NR1/NR3A receptors. Since physiological concentrations of the divalent cation Mg2+ did not affect the I–V dependence, our data suggest that relief of the voltage-dependent Ca2+ block of NR1/NR3A receptors by Zn2+ may be important for the regulation of excitatory glycinergic transmission, according to the Mg2+-block of conventional NR1/NR2 NMDA receptors.
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DOI：
10.1124/jpet.109.158493
发表时间：
2009-12-01
影响因子：
3.5
作者：
Smothers, C. Thetford;Woodward, John J.
通讯作者：
Woodward, John J.
DOI：
10.1523/jneurosci.4280-08.2009
发表时间：
2009-02-25
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Parnas M;Katz B;Lev S;Tzarfaty V;Dadon D;Gordon-Shaag A;Metzner H;Yaka R;Minke B
通讯作者：
Minke B
影响因子：
4.7
作者：
Laube, B;Schemm, R;Betz, H
通讯作者：
Betz, H
影响因子：
16.2
作者：
Grudzinska, J;Schemm, R;Laube, B
通讯作者：
Laube, B
影响因子：
3.6
作者：
Awobuluyi, Marc;Yang, Jin;Zhang, Dongxian
通讯作者：
Zhang, Dongxian