Disruption of KCC2 reveals an essential role of K-Cl cotransport already in early synaptic inhibition
Disruption of KCC2 reveals an essential role of K-Cl cotransport already in early synaptic inhibition
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DOI：
10.1016/s0896-6273(01)00297-5
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发表时间：
2001-05-01
期刊：
影响因子：
16.2
通讯作者：
Jentsch, TJ
中科院分区：
文献类型：
--
作者：
Hübner, CA;Stein, V;Jentsch, TJ
GABA和甘氨酸受体（配体门控阴离子通道）的突触抑制作用取决于氯离子的电化学电位。几种氯化钾协同转运蛋白可降低细胞内氯离子浓度[Cl-]（i），包括神经元亚型KCC 2。我们发现，KCC 2基因敲除小鼠出生后立即死亡，由于严重的运动缺陷，也取消了呼吸。坐骨神经记录显示异常的自发电活动和改变脊髓对外周电刺激的反应。在野生型动物的脊髓中，在抑制性突触处发现了KCC 2蛋白。膜片钳测量胚胎第18.5天的脊髓运动神经元表现出兴奋性GABA和甘氨酸的行动的情况下，但不存在，KCC 2，揭示了一个至关重要的作用，KCC 2的突触抑制。
Synaptic inhibition by GABA, and glycine receptors, which are ligand-gated anion channels, depends on the electrochemical potential for chloride. Several potassium-chloride cotransporters can lower the intracellular chloride concentration [Cl-](i), including the neuronal isoform KCC2. We show that KCC2 knockout mice died immediately after birth due to severe motor deficits that also abolished respiration. Sciatic nerve recordings revealed abnormal spontaneous electrical activity and altered spinal cord responses to peripheral electrical stimuli. In the spinal cord of wild-type animals, the KCC2 protein was found at inhibitory synapses. Patch-clamp measurements of embryonic day 18.5 spinal cord motoneurons demonstrated an excitatory GABA and glycine action in the absence, but not in the presence, of KCC2, revealing a crucial role of KCC2 for synaptic inhibition.