超极化激活的环核苷酸门控通道(HCN通道)抑制剂的研究进展

Research Progress on the Inhibitors of Hyperpolarization Activated Cyclic Nucleotide Gated Channels

超极化激活的环核苷酸门控通道(HCN通道)有四个亚型,分别为HCN1-4。HCN通道各亚型之间的基本结构相似,在许多组织中均有表达,其中以大脑和心脏组织中表达最为丰富。HCN通道既参与所在组织的正常生理功能,也与所在组织的病理状态密切相关。如神经损伤引起的神经源性疼痛常检测到HCN1通道表达量的增加,肥厚性心肌病和终末期心力衰竭等病理状态下常检测到心室肌细胞HCN4 mRNA及HCN2 mRNA表达增加。鉴于HCN通道与许多疾病密切相关,因此,以其为靶点来治疗相关疾病成为可能,但是由于HCN通道分布广泛,而目前该通道阻滞剂均为非选择性亚型抑制剂,临床应用时不可避免的引起副反应,因此发展选择性HCN通道亚型抑制剂就显得刻不容缓。本文就HCN通道抑制剂的研究发展做进一步探讨。

Hyperpolarization-activated cyclic nucleotide gated channels have four subtypes,named HCN1-HCN4,respectively.The HCN channels’ basic structure are similar,and are expressed in many tissues and organs.The most abundant expression of HCN channels is in the brain and heart tissue.HCN channels participate in the normal physiological function of the tissues,and are closely re-lated with the organization’s pathological state.Such as HCN1 mRNA expression is increased in the state of nerve injury-induced neu-ropathic pain,and HCN4 mRNA and HCN2 mRNA expression addition were often detected in pathological conditions of hypertrophic cardiomyopathy and end-stage heart failure ventricular cells.In view of the HCN channels are closely related to many diseases,therefore,it is possible to treat disease based on them.Due to the distribution of HCN channels far-ranging and its blockers non-selective,the side effects is unavoidable from clinical application.Therefore,the development of selective HCN channel subtype inhibitor is imperative.This article mainly reviews the features of HCN channels’ inhibitor.