NKCC1 downregulation induces hyperpolarizing shift of GABA responsiveness at near term fetal stages in rat cultured dorsal root ganglion neurons

BMC Neuroscience

Geert Callewaert²  Ludo Van Den Bosch¹  Karel Talavera³  Joelle N Chabwine⁴ 

[1] VIB, Vesalius Research Center, KU Leuven, Louvain, Belgium;Department of Cellular and Molecular Medicine, Katholieke Universiteit Leuven (KU Leuven), Louvain, Belgium;Laboratory of Ion Channel Research and TRP Channel Research Platform (TRPLe), Department of Cellular and Molecular Medicine, KU Leuven, Louvain, Belgium;Neurology Unit, Department of Medicine, Faculty of Sciences, University of Fribourg, Chemin du Musée, 5, Fribourg 1700, Switzerland

关键词: Fetal analgesia;    Oxytocin;    Bumetanide;    NKCC1;    Intracellular chloride;    GABA;    Dorsal root ganglion neurons;   

Others  :  1220309
DOI  :  10.1186/s12868-015-0180-4

 received in 2015-03-19, accepted in 2015-07-08,  发布年份 2015

【 摘 要 】

Background

GABA _Areceptor-mediated neurotransmission is greatly influenced by cation-chloride cotransporter activity during developmental stages. In embryonic neurons Na–K–2Cl (NKCC1) cotransporters mediate active chloride uptake, thus increasing the intracellular chloride concentration associated with GABA-induced depolarization. At fetal stages near term, oxytocin-induced NKCC1 downregulation has been implicated in the developmental shift from depolarizing to hyperpolarizing GABA action. Mature dorsal root ganglion neurons (DRGN), however, express high NKCC1 levels and maintain high intracellular chloride levels with consequent GABA-induced depolarization.

Results

Gramicidin-perforated patch-clamp recordings were used to assess the developmental change in chloride homeostasis in rat cultured small DRGN at the embryonic day 16 (E16) and 19 (E19). The results were compared to data previously obtained in fetal DRGN at E14 and in mature cells. A significant NKCC1 downregulation, leading to reduction in excitatory GABAergic transmission, was observed at E16 and E19.

Conclusion

These results indicate that NKCC1 activity transiently decreases in DRGN at fetal stages near term. This developmental shift in GABAergic transmission may contribute to fetal analgesia and neuroprotection at birth.

【 授权许可】

   
2015 Chabwine et al.

【 图 表 】

Figure1.

Figure2.

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