{"title":"内皮向内纠偏的K+通道是剪应力诱导的机械传导的关键组成部分。","authors":"Ibra S Fancher, Irena Levitan","doi":"10.1016/bs.ctm.2020.02.002","DOIUrl":null,"url":null,"abstract":"<p><p>It has been recognized for decades that fluid shear stress plays a major role in vascular function. Acting on the endothelium shear stress induces vasorelaxation of resistance arteries and plays a major role in the propensity of the major arteries to atherosclerosis. Many elements of shear-induced signaling have been identified yet we are just beginning to decipher the roles that mechanosensitive ion channels may play in the signaling pathways initiated by shear stress. Endothelial inwardly-rectifying K<sup>+</sup> channels were identified as potential primary mechanosensors in the late 1980s yet until our recent works, highlighted in the forthcoming chapter, the functional effect of a shear-activated K<sup>+</sup> current was completely unknown. In this chapter, we present the physiological effects of shear stress in arteries in health and disease and highlight the most prevalent of today's investigated mechanosensitive ion channels. Ultimately, we focus on Kir2.1 channels and discuss in detail our findings regarding the downstream signaling events that are induced by shear-activated endothelial Kir2.1 channels. Most importantly, we examine our findings regarding hypercholesterolemia-induced inhibition of Kir channel shear-sensitivity and the impact on endothelial function in the context of flow (shear)-mediated vasodilation and atherosclerosis.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.ctm.2020.02.002","citationCount":"5","resultStr":"{\"title\":\"Endothelial inwardly-rectifying K<sup>+</sup> channels as a key component of shear stress-induced mechanotransduction.\",\"authors\":\"Ibra S Fancher, Irena Levitan\",\"doi\":\"10.1016/bs.ctm.2020.02.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>It has been recognized for decades that fluid shear stress plays a major role in vascular function. Acting on the endothelium shear stress induces vasorelaxation of resistance arteries and plays a major role in the propensity of the major arteries to atherosclerosis. Many elements of shear-induced signaling have been identified yet we are just beginning to decipher the roles that mechanosensitive ion channels may play in the signaling pathways initiated by shear stress. Endothelial inwardly-rectifying K<sup>+</sup> channels were identified as potential primary mechanosensors in the late 1980s yet until our recent works, highlighted in the forthcoming chapter, the functional effect of a shear-activated K<sup>+</sup> current was completely unknown. In this chapter, we present the physiological effects of shear stress in arteries in health and disease and highlight the most prevalent of today's investigated mechanosensitive ion channels. Ultimately, we focus on Kir2.1 channels and discuss in detail our findings regarding the downstream signaling events that are induced by shear-activated endothelial Kir2.1 channels. Most importantly, we examine our findings regarding hypercholesterolemia-induced inhibition of Kir channel shear-sensitivity and the impact on endothelial function in the context of flow (shear)-mediated vasodilation and atherosclerosis.</p>\",\"PeriodicalId\":11029,\"journal\":{\"name\":\"Current topics in membranes\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2020-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/bs.ctm.2020.02.002\",\"citationCount\":\"5\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current topics in membranes\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/bs.ctm.2020.02.002\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2020/3/23 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current topics in membranes","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/bs.ctm.2020.02.002","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/3/23 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
Endothelial inwardly-rectifying K+ channels as a key component of shear stress-induced mechanotransduction.
It has been recognized for decades that fluid shear stress plays a major role in vascular function. Acting on the endothelium shear stress induces vasorelaxation of resistance arteries and plays a major role in the propensity of the major arteries to atherosclerosis. Many elements of shear-induced signaling have been identified yet we are just beginning to decipher the roles that mechanosensitive ion channels may play in the signaling pathways initiated by shear stress. Endothelial inwardly-rectifying K+ channels were identified as potential primary mechanosensors in the late 1980s yet until our recent works, highlighted in the forthcoming chapter, the functional effect of a shear-activated K+ current was completely unknown. In this chapter, we present the physiological effects of shear stress in arteries in health and disease and highlight the most prevalent of today's investigated mechanosensitive ion channels. Ultimately, we focus on Kir2.1 channels and discuss in detail our findings regarding the downstream signaling events that are induced by shear-activated endothelial Kir2.1 channels. Most importantly, we examine our findings regarding hypercholesterolemia-induced inhibition of Kir channel shear-sensitivity and the impact on endothelial function in the context of flow (shear)-mediated vasodilation and atherosclerosis.
期刊介绍:
Current Topics in Membranes provides a systematic, comprehensive, and rigorous approach to specific topics relevant to the study of cellular membranes. Each volume is a guest edited compendium of membrane biology.