膜超极化激活离子通道及其靶向抗癫痫药物研究进展

癫痫是一种较为常见的神经系统疾病，主要以大量神经元同步异常放电为特征。目前普遍认为，神经元或神经网络兴奋性和抑制性 电信号传输的失衡，是癫痫发病的最根本原因。现有的抗癫痫药物主要以钠离子通道、钙离子通道、钾离子通道、谷氨酸受体和γ-氨基丁 酸离子通道为靶点，但接受这些药物治疗后，仍有近1/3的病人无法控制癫痫发作。因此，抗癫痫药物的研发亟需新靶点和新思路。许多 研究证据表明，膜超极化激活离子通道的基因突变可以导致遗传型癫痫的发作，且在脑部损伤后，膜超极化激活离子通道会发生表达水平、 通道生物物理学性质及通道亚基构成的改变，从而增加神经元和神经网络兴奋性，促使癫痫发病。故近年来，膜超极化激活离子通道及其 靶向抗癫痫药物研究引起人们广泛关注。综述膜超极化激活离子通道与癫痫发病之间的关系，并探讨以膜超极化激活离子通道为靶点进行 抗癫痫药物开发和治疗的可行性。

Progress in Research of Hyperpolarization-activated Cation Non-selective Channels and Antiepileptic Drugs Targeting the Channels

Epilepsy is a common neurological disorder characterized mainly by synchronous abnormal firing of a large number of neurons . It is now widely accepted that the imbalance between the excitatory and inhibitory synaptic transmission is the underlying pathogenesis of epilepsy. One third of epilepsy patients failed to response to the available treatments which mainly target sodium channels, calcium channels, potassium channels, glutamate receptors and GABA channels. Thus, the new targets and new ideas are urgently needed for antiepileptic drug development. More and more researches have suggested that the single-point mutation in hyperpolarization-activated cation non-selective channels(HCN channels) is able to induce genetic epilepsy. In addition, the changes in expression level, biophysical properties and subunit composition of HCN channels after brain injury contribute to epileptogenesis. Therefore, HCN channels and antiepileptic drugs targeting the channels have drawn much attention in recent years.In this article, the changes in HCN channels in epilepsy were summarized and the feasibility of antiepileptic drug development and treatment targeting HCN channels was discussed.