Regulation of ion channels in the microcirculation by mineralocorticoid receptor activation.

4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology
Current topics in membranes Pub Date : 2020-01-01 Epub Date: 2020-02-29 DOI:10.1016/bs.ctm.2020.02.001
Laura Chambers, Anne M Dorrance
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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.

矿物皮质激素受体激活对微循环离子通道的调节。
矿盐皮质激素受体(MR)在肾上皮中调节钠和水平衡以及随后的血压中的作用已被经典地研究过。然而,MR也通过调节离子通道的表达和功能在微血管中发挥关键作用。由其内源性激动剂醛固酮激活MR导致MR易位进入细胞核,在那里它可以作为转录因子。虽然醛固酮的大部分作用可以通过MR激活归因于其基因组活性,但它也可以通过非基因组机制起作用。这种普遍存在的受体的激活增加了上皮钠通道(ENaC)在周围血管和脑血管的内皮细胞和平滑肌细胞中的表达。MR激活还调节钙通道、钙活化钾通道和各种瞬时受体电位(TRP)通道的活性。这些离子通道的改变会导致无数的负面后果,包括内皮依赖性血管舒张受损、肌原性张力的产生改变、炎症和氧化应激的增加。综上所述,这些研究表明了研究MR对血管中离子通道功能影响的重要性。虽然近年来该领域的研究取得了进展,但仍有许多巨大的知识空白需要填补。关键的未来研究方向包括确定参与这种相互作用的分子机制,以及阐明可能存在的潜在性别差异,因为这些领域的理解目前还缺乏。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current topics in membranes
Current topics in membranes 生物-生化与分子生物学
CiteScore
3.50
自引率
0.00%
发文量
10
审稿时长
>12 weeks
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.
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