Nonsynaptic glycine release is involved in the early KCC2 expression
Nonsynaptic glycine release is involved in the early KCC2 expression
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DOI：
10.1002/dneu.22358
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发表时间：
2016-07-01
影响因子：
3
通讯作者：
Branchereau, Pascal
中科院分区：
文献类型：
--
作者：
Allain, Anne-Emilie;Cazenave, William;Branchereau, Pascal
阳离子-氯离子协同转运蛋白是细胞 Cl-稳态的重要调节剂。其中，Na+-K+-2Cl(-)协同转运蛋白（NKCC1）负责大多数未成熟大脑结构中细胞内氯离子的积累，而K+-Cl-协同转运蛋白（KCC2）则从成熟神经元中排出氯离子，确保氯离子介导的GABA/甘氨酸的抑制作用。我们已经证明 KCC2 和 NKCC1 在胚胎早期 (E11.5) 的腹侧脊髓 (SC) 中表达。 KCC2 过早表达的机制尚不清楚。在这项研究中，我们发现士的宁长期阻断甘氨酸受体 (GlyR) 会导致 KCC2 表达丧失，但不会影响 NKCC1 水平。这种效应并不依赖于 Na+ 动作电位的激发，而是由 Ca2+ 依赖性 PKC 阻滞剂模拟。阻断神经递质的囊泡释放不会影响马钱子碱效应，而阻断体积敏感的外向整流（VSOR）氯离子通道会重现 GlyR 阻断，这表明 KCC2 受到未成熟腹侧脊髓网络中放射状祖细胞释放甘氨酸的控制。最后，我们证明士的宁治疗阻止了节律性自发活动的成熟。因此，GlyR 激活是功能性脊髓运动网络表达的必要发育过程。 (c) 2015 年 Wiley periodicals, Inc. 开发 Neurobiol 76: 764-779, 2016
The cation-chloride co-transporters are important regulators of the cellular Cl- homeostasis. Among them the Na+-K+-2Cl(-) co-transporter (NKCC1) is responsible for intracellular chloride accumulation in most immature brain structures, whereas the K+-Cl- co-transporter (KCC2) extrudes chloride from mature neurons, ensuring chloride-mediated inhibitory effects of GABA/glycine. We have shown that both KCC2 and NKCC1 are expressed at early embryonic stages (E11.5) in the ventral spinal cord (SC). The mechanisms by which KCC2 is prematurely expressed are unknown. In this study, we found that chronically blocking glycine receptors (GlyR) by strychnine led to a loss of KCC2 expression, without affecting NKCC1 level. This effect was not dependent on the firing of Na+ action potentials but was mimicked by a Ca2+-dependent PKC blocker. Blocking the vesicular release of neurotransmitters did not impinge on strychnine effect whereas blocking volume-sensitive outwardly rectifying (VSOR) chloride channels reproduced the GlyR blockade, suggesting that KCC2 is controlled by a glycine release from progenitor radial cells in immature ventral spinal networks. Finally, we showed that the strychnine treatment prevented the maturation of rhythmic spontaneous activity. Thereby, the GlyR-activation is a necessary developmental process for the expression of functional spinal motor networks. (c) 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 764-779, 2016