Deficits in GABAergic inhibition result in the abnormal neuronal activation and synchronization that underlies seizures. However, the molecular mechanisms responsible for transforming a normal brain into an epileptic one remain largely unknown. Hyperpolarizing inhibition mediated by type A GABA (GABAA) receptors is dependent on chloride extrusion by the neuron-specific type 2K+-Cl- cotransporter (KCC2). Loss-of-function mutations in KCC2 are a known cause of infantile epilepsy in humans and KCC2 dysfunction is present in patients with both idiopathic and acquired epilepsy. Here we discuss the growing evidence that KCC2 dysfunction has a central role in the development and severity of the epilepsies.

中文翻译：

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控制 KCC2：癫痫的新治疗靶点

GABA 能抑制的缺陷导致异常的神经元激活和同步，这是癫痫发作的基础。然而，负责将正常大脑转变为癫痫大脑的分子机制在很大程度上仍然未知。由 A 型 GABA (GABAA) 受体介导的超极化抑制依赖于神经元特异性 2K+-Cl-协同转运蛋白 (KCC2) 的氯化物挤出。KCC2 功能丧失突变是人类婴儿癫痫的已知原因，特发性和获得性癫痫患者都存在 KCC2 功能障碍。在这里，我们讨论了越来越多的证据，即 KCC2 功能障碍在癫痫的发展和严重程度中起着核心作用。