Ion channels and channelopathies in glomeruli.

IF 29.9 1区 医学 Q1 PHYSIOLOGY
Physiological reviews Pub Date : 2023-01-01 Epub Date: 2022-08-25 DOI:10.1152/physrev.00013.2022
Alexander Staruschenko, Rong Ma, Oleg Palygin, Stuart E Dryer
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引用次数: 10

Abstract

An essential step in renal function entails the formation of an ultrafiltrate that is delivered to the renal tubules for subsequent processing. This process, known as glomerular filtration, is controlled by intrinsic regulatory systems and by paracrine, neuronal, and endocrine signals that converge onto glomerular cells. In addition, the characteristics of glomerular fluid flow, such as the glomerular filtration rate and the glomerular filtration fraction, play an important role in determining blood flow to the rest of the kidney. Consequently, disease processes that initially affect glomeruli are the most likely to lead to end-stage kidney failure. The cells that comprise the glomerular filter, especially podocytes and mesangial cells, express many different types of ion channels that regulate intrinsic aspects of cell function and cellular responses to the local environment, such as changes in glomerular capillary pressure. Dysregulation of glomerular ion channels, such as changes in TRPC6, can lead to devastating glomerular diseases, and a number of channels, including TRPC6, TRPC5, and various ionotropic receptors, are promising targets for drug development. This review discusses glomerular structure and glomerular disease processes. It also describes the types of plasma membrane ion channels that have been identified in glomerular cells, the physiological and pathophysiological contexts in which they operate, and the pathways by which they are regulated and dysregulated. The contributions of these channels to glomerular disease processes, such as focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy, as well as the development of drugs that target these channels are also discussed.

肾小球中的离子通道和通道病。
肾脏功能的一个重要步骤是形成超滤液,并输送到肾小管进行后续处理。这一过程被称为肾小球滤过,由内在调节系统以及汇聚到肾小球细胞的旁分泌、神经元和内分泌信号控制。此外,肾小球液体流动的特征,如肾小球滤过率和肾小球滤过分数,在决定肾脏其他部位的血流量方面起着重要作用。因此,最初影响肾小球的疾病过程最有可能导致终末期肾衰竭。构成肾小球过滤器的细胞,尤其是荚膜细胞和系膜细胞,表达多种不同类型的离子通道,这些通道可调节细胞功能的内在方面以及细胞对局部环境的反应,如肾小球毛细血管压力的变化。肾小球离子通道失调(如 TRPC6 的变化)可导致破坏性肾小球疾病,而包括 TRPC6、TRPC5 和各种离子受体在内的许多通道都是很有希望的药物开发靶点。本综述讨论了肾小球结构和肾小球疾病过程。它还描述了已在肾小球细胞中发现的质膜离子通道类型、它们工作的生理和病理生理环境,以及它们被调节和失调的途径。还讨论了这些通道对局灶节段性肾小球硬化症(FSGS)和糖尿病肾病等肾小球疾病过程的贡献,以及针对这些通道的药物的开发。
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来源期刊
Physiological reviews
Physiological reviews 医学-生理学
CiteScore
56.50
自引率
0.90%
发文量
53
期刊介绍: Physiological Reviews is a highly regarded journal that covers timely issues in physiological and biomedical sciences. It is targeted towards physiologists, neuroscientists, cell biologists, biophysicists, and clinicians with a special interest in pathophysiology. The journal has an ISSN of 0031-9333 for print and 1522-1210 for online versions. It has a unique publishing frequency where articles are published individually, but regular quarterly issues are also released in January, April, July, and October. The articles in this journal provide state-of-the-art and comprehensive coverage of various topics. They are valuable for teaching and research purposes as they offer interesting and clearly written updates on important new developments. Physiological Reviews holds a prominent position in the scientific community and consistently ranks as the most impactful journal in the field of physiology.
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