Understanding structure and function of acid-sensing ion channels
会议名称：《中国神经科学学会第九届全国学术会议暨第五次会员代表大会》
会议日期：2011年
学科分类：0710[理学-生物学] 07[理学] 071006[理学-神经生物学]
摘 要：The acid-sensing ion channel(ASIC) has a prominent role in tissue pH-sensing and neuronal signalling. Subunits of ASICs are members of the degenerin/epithelial Na channel protein *** date,seven ASIC subunits have been identified:ASIC1a,ASIC1b,ASIC1b2,ASIC2a,ASIC2b,ASIC3,and *** subunit contains cytosolic N and C termini,two alpha-helical transmembrane domains(M1-M2),and a disulfide-rich multidomain extracellular *** form a variety of homo- and heterotrimeric ion channels that are activated by extracellular acidosis associated with neurotransmission,injury,inflammation and ischemia,triggering membrane depolarization via Na influx into target *** the operating mechanisms of these ion channels could therefore provide the catalyst for further studying ASIC physiology and pharmacology,as well as promoting the development of experimental techniques for other families of ion channels and/or *** this talk,I will present our current work on ASIC structure and function,in particular those of ASIC1a and ASIC3 *** in this area has been stimulated in recent years by the publication of high-resolution structures of ASIC1,which have permitted the structure-directed approaches and the creation of ASIC homology models.I will first discuss the crucial roles of ASICs in mediating neuronal injury and pain *** a series of computational,chemical and functional approaches,and nonproton ligands(GMQ,agmatine and amiloride) as probes,I will then delineate the nonproton ligand sensing domain in ASIC3 channels at the atomic level and describe how chemical biology,homology modeling and ligand docking can provide useful information about ligand interactions.I will also consider some of the ongoing projects in my laboratory that are investigating the pathophysiological roles of ASICs using ASIC subunit gene knockout *** report ends with a discussion on the generality of ASICs as a model system for the study of struc