Induction of NMDA and GABAA receptor-mediated Ca2+ oscillations with KCC2 mRNA downregulation in injured facial motoneurons
Induction of NMDA and GABAA receptor-mediated Ca2+ oscillations with KCC2 mRNA downregulation in injured facial motoneurons
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DOI：
10.1152/jn.00721.2002
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发表时间：
2003-03-01
影响因子：
2.5
通讯作者：
Fukuda, A
中科院分区：
文献类型：
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作者：
Toyoda, H;Ohno, K;Fukuda, A
为了阐明γ-氨基丁酸A型（GABA（A））受体介导的作用发生的变化，并有助于神经元损伤后网络活动的改变，我们研究了大鼠面神经横断模型中细胞内Ca 2+浓度（[Ca 2 +]（i））的动态变化。在面运动神经元中，轴突切断引起静息[Ca 2 +]（i）、GABA介导的[Ca 2 +]（i）瞬变、谷氨酸诱发的[Ca 2 +]（i）增加的增强和自发的[Ca 2 +]（i）振荡的升高。GABA（A）受体拮抗剂荷包牡丹碱和N-甲基-D-天冬氨酸（NMDA）受体拮抗剂D（-）-2-氨基-5-膦酰基戊酸可阻断轴突切断引起的这些变化。轴突切断还可引起K+-Cl-协同转运体（KCC 2）mRNA表达下调、细胞内Cl-浓度（[Cl-]（i））升高和GABA能超极化向去极化转变。我们认为，在轴突切断的神经元中，KCC 2下调损害Cl-稳态，使GABA去极化，导致内源性GABA通过促进NMDA受体激活诱导[Ca ~（2+）]（i）振荡。这种GABA（A）受体介导的[Ca 2 +]（i）振荡可能在神经存活和再生中起作用。
To clarify the changes that occur in gamma-aminobutyric acid type A (GABA(A)) receptor-mediated effects and contribute to alterations in the network activities after neuronal injury, we studied intracellular Ca2+ concentration ([Ca2+](i)) dynamics in a rat facial-nerve-transection model. In facial motoneurons, an elevation of the resting [Ca2+](i), GABA-mediated [Ca2+](i) transients, enhancement of the glutamate-evoked [Ca2+](i) increases, and spontaneous [Ca2+](i) oscillations were induced by axotomy. All these axotomy-induced modifications were abolished by the GABA(A)-receptor antagonist bicuculline and N-methyl-D-aspartate (NMDA)-receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid. A downregulation of K+-Cl- cotransporter (KCC2) mRNA, an increase in intracellular Cl- concentration ([Cl-](i)), and transformation of GABAergic hyperpolarization to depolarization were also induced by axotomy. We suggest that in axotomized neurons KCC2 downregulation impairs Cl- homeostasis and makes GABA act depolarizing, resulting in endogenous GABA inducing [Ca2+](i) oscillations via facilitation of NMDA-receptor activation. Such GABA(A)-receptor-mediated [Ca2+](i) oscillations may play a role in neural survival and regeneration.