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KCC2, epileptiform synchronization, and epileptic disorders
Progress in Neurobiology ( IF 6.7 ) Pub Date : 2017-12-02 , DOI: 10.1016/j.pneurobio.2017.11.002
Graziella Di Cristo , Patricia N. Awad , Shabnam Hamidi , Massimo Avoli

The K+-Cl co-transporter KCC2 is a neuron-specific, Cl extruder that uses K+ gradient for maintaining low intracellular [Cl]. It is indeed well established that sustaining an outwardly-directed electrochemical Cl gradient across the neuronal membrane is fundamental for a proper function of postsynaptic GABAA receptor signaling. In particular, studies in the last two decades have shown that KCC2 activity is important to maintain a hyperpolarizing GABAergic neurotransmission. Conversely, low KCC2 activity should lead to depolarizing, and under specific conditions, excitatory GABAergic transmission. Not surprisingly given the critical role of KCC2 in regulating the inhibitory drive, alterations in its expression levels and activity are linked with epilepsy. Here, we will first summarize data regarding the role of KCC2 in epileptiform synchronization. Next, we will review evidence indicating that KCC2 expression and function are altered in chronic epileptic disorders, both in the developing and adult brain. We will also go through recent findings regarding the molecular mechanisms underlying the changes in KCC2 activity that occur following seizures. Finally, we will consider the modulation of KCC2 function as a potential, novel therapeutic target for the treatment of epileptic disorders.



中文翻译:

KCC2,癫痫样同步化和癫痫病

在K + -Cl -共转运KCC2是神经元特异性的,氯-挤出机,它使用ķ +梯度用于维持低的细胞内[氯- ]。这的确是公认的是维持一个向外指向的电化学氯-跨越神经元膜梯度为突触后GABA的适当的功能根本受体信号传导。特别是最近二十年来的研究表明,KCC2活性对于维持超极化的GABA能神经传递很重要。相反,低的KCC2活性应导致去极化,并在特定条件下引起兴奋性GABA能传递。毫不奇怪,鉴于KCC2在调节抑制性驱动中的关键作用,其表达水平和活性的改变与癫痫有关。在这里,我们将首先总结有关KCC2在癫痫样同步中的作用的数据。接下来,我们将审查证据,这些证据表明在发育中和成年大脑的慢性癫痫病中,KCC2的表达和功能均发生了改变。我们还将浏览有关癫痫发作后发生的KCC2活性变化的分子机制的最新发现。

更新日期:2017-12-02
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