细胞外调控分子对酸敏感离子通道的功能调控及其机制

酸敏感离子通道(acid-Sensing ion channels,ASlCs)是一类由细胞外质子(H )激活的配体门控阳离子通道.迄今为止,人们在哺乳动物体内已经发现了6种ASICs亚基蛋白,它们分布在多种组织器官中.越来越多的研究表明:ASICs参与了机体的生理、病理过程,如:学习、记忆、痛觉、脑中风和肿瘤.在过去的10年中,人们发现多种内源性或外源性分子可以调控ASICs通道活性.由于这些细胞外调控分子与多种生理和病理功能有关,因此研究细胞外调控分子对ASICs的调控及其分子机制,可以帮助我们更多地了解ASICs功能以及结构信息,也为人们设计ASICs靶点特异性药物提供了理论依据.文章将系统地介绍细胞外调控分子对ASICs的功能调控及其作用机制,特别是该研究领域的最新进展.

Functional Modulation of Acid-sensing Ion Channels by Extracellular Modulators and Their Mechanisms

Acid-sensing ion channels (ASICs) are amiloride-sensitive ligand-gated cation channels that are activated by extracellular protons (H⁺). To date, six ASIC subunits have been identified and shown to broadly distribute in mammalian tissues and organs. Increasing evidence has highlighted the role of ASICs in various physiological and pathological processes such as learning and memory, pain sensation, ischemic stroke and tumor. In addition to the accepted activator of ASICs H⁺, a variety of extracellular modulators that regulate the activity of these channels have been characterized in past ten years. These extracellular modulators are involved in various physiological and pathological processes, therefore, delineating the modulation of ASICs by extracellular modulators and their molecular mechanisms will contribute to the better understanding of the precise physiological and pathological functions of these channels, and provide the clues of structure information, which is helpful to the design of novel drugs that specifically target these channels. This paper is to give a comprehensive review of the modulation of ASICs activity by extracellular modulators and the underlying mechanisms, especially focusing on the newly progress in this research filed in past few years.