Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK; Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA.
Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA.
Trends Neurosci. 2017 Sep;40(9):555-571. doi: 10.1016/j.tins.2017.06.008. Epub 2017 Aug 10.
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 (GABA) 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.
GABA 能抑制的缺乏导致了癫痫发作的基础，即异常的神经元激活和同步。然而，将正常大脑转变为癫痫的分子机制在很大程度上仍然未知。由 A 型 GABA（GABA）受体介导的超极化抑制依赖于神经元特异性 2K-Cl 共转运体（KCC2）的氯离子外排。KCC2 的功能丧失突变是人类婴儿癫痫的已知原因，并且 KCC2 功能障碍存在于特发性和获得性癫痫患者中。在这里，我们讨论了越来越多的证据表明 KCC2 功能障碍在癫痫的发展和严重程度中起核心作用。
