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电压门控离子通道与癫痫:回路功能障碍与治疗。

Voltage-gated ion channels in epilepsies: circuit dysfunctions and treatments.

机构信息

Aix-Marseille University, INSERM, UNIS, Marseille, France.

Aix-Marseille University, INSERM, UNIS, Marseille, France.

出版信息

Trends Pharmacol Sci. 2024 Nov;45(11):1018-1032. doi: 10.1016/j.tips.2024.09.004. Epub 2024 Oct 14.

Abstract

Epileptic encephalopathies are generally considered to be functional disruptions in the balance between neural excitation and inhibition. Excitatory and inhibitory voltage-gated ion channels are key targets of antiepileptic drugs, playing a critical role in regulating neuronal excitation and synaptic transmission. Recent research has highlighted the significance of ion channels in various aspects of epilepsy, including presynaptic neurotransmitter release, intrinsic neuronal excitability, and neural synchrony. Genetic alterations in excitatory and inhibitory ion channels within principal neurons and in inhibitory interneurons have also been identified as key contributors to the development of epilepsies. We review these recent studies and shed light on the bidirectional relationship between epilepsy and neuronal excitability and the latest advancements in pharmacological therapeutics targeting ion channels for epilepsy treatment.

摘要

癫痫性脑病通常被认为是神经兴奋与抑制之间平衡的功能紊乱。兴奋性和抑制性电压门控离子通道是抗癫痫药物的关键靶点,在调节神经元兴奋和突触传递方面发挥着重要作用。最近的研究强调了离子通道在癫痫的各个方面的重要性,包括突触前神经递质释放、内在神经元兴奋性和神经同步。主要神经元中的兴奋性和抑制性离子通道以及抑制性中间神经元中的遗传改变也被确定为癫痫发生的关键因素。我们回顾了这些最近的研究,并阐明了癫痫与神经元兴奋性之间的双向关系,以及针对癫痫治疗的离子通道药理学治疗的最新进展。

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