{"title":"Regulation of ion channels in the microcirculation by mineralocorticoid receptor activation.","authors":"Laura Chambers, Anne M Dorrance","doi":"10.1016/bs.ctm.2020.02.001","DOIUrl":null,"url":null,"abstract":"<p><p>The mineralocorticoid receptor (MR) has classically been studied in the renal epithelium for its role in regulating sodium and water balance and, subsequently, blood pressure. However, the MR also plays a critical role in the microvasculature by regulating ion channel expression and function. Activation of the MR by its endogenous agonist aldosterone results in translocation of the MR into the nucleus, where it can act as a transcription factor. Although most of the actions of the aldosterone can be attributed to its genomic activity though MR activation, it can also act by nongenomic mechanisms. Activation of this ubiquitous receptor increases the expression of epithelial sodium channels (ENaC) in both the endothelium and smooth muscle cells of peripheral and cerebral vessels. MR activation also regulates activity of calcium channels, calcium-activated potassium channels, and various transient receptor potential (TRP) channels. Modification of these ion channels results in a myriad of negative consequences, including impaired endothelium-dependent vasodilation, alterations in generation of myogenic tone, and increased inflammation and oxidative stress. Taken together, these studies demonstrate the importance of studying the impact of the MR on ion channel function in the vasculature. While research in this area has made advances in recent years, there are still many large gaps in knowledge that need to be filled. Crucial future directions of study include defining the molecular mechanisms involved in this interaction, as well as elucidating the potential sex differences that may exist, as these areas of understanding are currently lacking.</p>","PeriodicalId":11029,"journal":{"name":"Current topics in membranes","volume":" ","pages":"151-185"},"PeriodicalIF":0.0000,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.ctm.2020.02.001","citationCount":"3","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current topics in membranes","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/bs.ctm.2020.02.001","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/2/29 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 3
Abstract
The mineralocorticoid receptor (MR) has classically been studied in the renal epithelium for its role in regulating sodium and water balance and, subsequently, blood pressure. However, the MR also plays a critical role in the microvasculature by regulating ion channel expression and function. Activation of the MR by its endogenous agonist aldosterone results in translocation of the MR into the nucleus, where it can act as a transcription factor. Although most of the actions of the aldosterone can be attributed to its genomic activity though MR activation, it can also act by nongenomic mechanisms. Activation of this ubiquitous receptor increases the expression of epithelial sodium channels (ENaC) in both the endothelium and smooth muscle cells of peripheral and cerebral vessels. MR activation also regulates activity of calcium channels, calcium-activated potassium channels, and various transient receptor potential (TRP) channels. Modification of these ion channels results in a myriad of negative consequences, including impaired endothelium-dependent vasodilation, alterations in generation of myogenic tone, and increased inflammation and oxidative stress. Taken together, these studies demonstrate the importance of studying the impact of the MR on ion channel function in the vasculature. While research in this area has made advances in recent years, there are still many large gaps in knowledge that need to be filled. Crucial future directions of study include defining the molecular mechanisms involved in this interaction, as well as elucidating the potential sex differences that may exist, as these areas of understanding are currently lacking.
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.