NKCC1 downregulation induces hyperpolarizing shift of GABA responsiveness at near term fetal stages in rat cultured dorsal root ganglion neurons.
NKCC1 downregulation induces hyperpolarizing shift of GABA responsiveness at near term fetal stages in rat cultured dorsal root ganglion neurons.
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DOI：
10.1186/s12868-015-0180-4
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发表时间：
2015-07-14
期刊：
影响因子：
2.4
通讯作者：
Callewaert G
中科院分区：
文献类型：
--
作者：
Chabwine JN;Talavera K;Van Den Bosch L;Callewaert G
在发育阶段，GABAA受体介导的神经传递受到阳离子-氯化物协同转运体活性的极大影响。在胚胎神经元中，Na-K-2Cl（NKCC 1）协同转运蛋白介导活性氯摄取，从而增加与GABA诱导的去极化相关的细胞内氯浓度。在胎儿期近术语，催产素诱导的NKCC 1下调已牵连在从去极化到超极化GABA行动的发展转变。然而，成熟的背根神经节神经元（DRGN）表达高水平的NKCC 1，并保持高的细胞内氯离子水平与随后的GABA诱导的去极化。采用短杆菌肽穿孔膜片钳技术，观察了胚胎第16天和第19天（E16和E19）培养的大鼠小DRGN氯稳态的发育变化。将结果与先前在E14胎儿DRGN和成熟细胞中获得的数据进行比较。在E16和E19时观察到NKCC 1显著下调，导致兴奋性GABA能传递减少。这些结果表明，NKCC 1活性在DRGN中在胎儿期近足月时短暂降低。这种GABA能传递的发育转变可能有助于胎儿分娩时的镇痛和神经保护。
GABAA receptor-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. 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. 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.