期刊
DEVELOPMENTAL NEUROBIOLOGY
卷 76, 期 7, 页码 764-779出版社
WILEY-BLACKWELL
DOI: 10.1002/dneu.22358
关键词
development; embryo; spinal cord; rhythmic spontaneous activity; glycine receptor; motor network; radial cell; chloride co-transporter
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
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