钾通道作为癫痫治疗的重要靶点和工具。

Potassium channels as prominent targets and tools for the treatment of epilepsy.

作者信息

Nikitin E S, Vinogradova L V

机构信息

Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia.

出版信息

Expert Opin Ther Targets. 2021 Mar;25(3):223-235. doi: 10.1080/14728222.2021.1908263. Epub 2021 Apr 6.

Abstract

INTRODUCTION

K channels are of great interest to epilepsy research as mutations in their genes are found in humans with inherited epilepsy. At the level of cellular physiology, K+ channels control neuronal intrinsic excitability and are the main contributors to membrane repolarization of active neurons. Recently, a genetically modified voltage-dependent K channel has been patented as a remedy for epileptic seizures.

AREAS COVERED

We review the role of potassium channels in excitability, clinical and experimental evidence for the association of potassium channelopathies with epilepsy, the targeting of K+ channels by drugs, and perspectives of gene therapy in epilepsy with the expression of extra K+ channels in the brain.

EXPERT OPINION

Control over K+ conductance is of great potential benefit for the treatment of epilepsy. Nowadays, gene therapy affecting K+ channels is one of the most promising approaches to treat pharmacoresistant focal epilepsy.

摘要

引言

钾通道在癫痫研究中备受关注,因为在遗传性癫痫患者中发现了其基因突变。在细胞生理学层面,钾离子通道控制神经元的内在兴奋性,是活跃神经元膜复极化的主要因素。最近,一种基因改造的电压依赖性钾通道已获专利,作为癫痫发作的治疗方法。

涵盖领域

我们综述了钾通道在兴奋性中的作用、钾通道病与癫痫关联的临床和实验证据、药物对钾离子通道的靶向作用,以及通过在大脑中表达额外的钾离子通道进行癫痫基因治疗的前景。

专家观点

控制钾离子电导对癫痫治疗具有巨大的潜在益处。如今,影响钾离子通道的基因治疗是治疗药物难治性局灶性癫痫最有前景的方法之一。

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