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HCN通道在癫痫中的作用
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Abstract:
癫痫是一种大脑神经元反复异常放电所致的短暂性脑功能障碍的慢性神经系统疾病。中枢神经系统兴奋性谷氨酸能与抑制性γ-氨基丁酸能神经递质间的平衡紊乱和促离子型受体等离子通道功能的改变可直接诱导癫痫发作。研究表明超极化激活的环核苷酸阳离子通道(Hyperpolarization activates cyclic nucleotidegated channels, HCN)具有兴奋和抑制两种不同的功能状态，HCN通道通过对膜电位、膜电阻和神经元兴奋性进行调节参与中枢神经系统疾病的病理生理过程。HCN通道突变、辅助亚基TRIP8b缺失和HCN通道抑制均与癫痫发作相关。本文将重点阐述HCN通道作用于癫痫的神经细胞和分子生物学机制，有助于更有效的对症治疗癫痫，并减少治疗的副作用，并为进一步研发新的抗癫痫药物的靶向干预治疗开辟新的途径和策略。
Epilepsy is a chronic neurological disease characterized by a transient brain dysfunction due to repeated abnormal discharges of brain neurons. The imbalance between excitatory glutamate and inhibitory gamma-aminobutyric acid (GABA) neurotransmitter in the central nervous system and changes in ionic functions of ionotropic receptors directly induce epileptic seizures. Accumulating evidence suggests that hyperpolarization activates cyclic nucleotide-gated channels (HCN) have ex-citatory and inhibitory functional states. HCN channels are widely implicated in pathophysiological process of specific nervous diseases through regulating membrane potential and membrane resistance as well as excitability of neurons. Mutation, deletion of auxiliary subunit TRIP8b and inhibition of HCN channel were associated with epileptic seizures. This review focuses on the molecular and cellular mechanisms of the protective effect of HCN channel on epilepsy, which may help to treat the symptoms more effectively and reduce the side effects of treatment, aiming at providing new strategies and ideas of new antiepileptic drugs for the targeted intervention therapy of epilepsy.
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