双孔钾通道TREK-1中枢神经系统药理学研究进展  

Progress in understanding the central nervous system pharmacology of the two-pore domain potassium channel TREK-1

作　　者：单金凤 王伟平 王晓良[1] SHAN Jin-feng;WANG Wei-ping;WANG Xiao-liang(Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院、北京协和医学院药物研究所,北京100050

出　　处：《药学学报》2020年第7期1357-1363,共7页Acta Pharmaceutica Sinica

基　　金：重大新药创制科技重大专项(2018ZX09711001-004-004)。

摘　　要：双孔钾离子通道(two-pore domain potassium channels,K2P)是20世纪90年代发现的一类钾离子通道亚家族,其中TREK-1是研究最为广泛的一种K2P亚型。TREK-1广泛存在于机体内,特别是在中枢神经系统中高表达,它的主要作用是控制细胞兴奋性并维持膜电位低于去极化阈值,因此参与调节多种生理和病理过程。TREK-1也是多种疾病潜在的药物作用靶标,很多已上市药物可影响TREK-1的功能,但目前缺少特异性的TREK-1调节剂和以TREK-1为靶点的药物。本文在介绍TREK-1的结构、分布以及调控的基础上,重点介绍近年来TREK-1在神经保护、癫痫、抑郁以及麻醉等方面的药理学研究进展和相关的TREK-1调节剂的研究现状。Two-pore domain potassium channels(K2P)make up a subfamily of potassium channels discovered in the 1990s,and TREK-1 is the most widely studied subtype of K2P.TREK-1 is widely expressed in the body and especially in the central nervous system,where its main role is to control cell excitability and maintain the membrane potential below the depolarization threshold.It thereby participates in regulating various physiological and pathological processes.TREK-1 is also a potential drug target in many diseases.It is known that many marketed drugs can affect the function of TREK-1,but currently there are no specific TREK-1 modulators or drugs.We review the structure,distribution and regulation of TREK-1 and focus on recent progress in understanding the pharmacology of TREK-1 and its role in neuroprotection,depression,anesthesia and epilepsy.The research status of TREK-1 modulators is discussed.

关 键 词：双孔钾通道 TREK-1 神经保护 癫痫 抑郁 麻醉 

分 类 号：R964[医药卫生—药理学]