Lessons learned about epithelial sodium channels from transgenic mouse models

Abstract

Purpose of reviewThis review provides an up-to-date understanding about the regulation of epithelial sodium channel (ENaC) expression and function. In particular, we will focus on its implication in renal Na+ and K+ handling and control of blood pressure using transgenic animal models.Recent findingsIn kidney, the highly amiloride-sensitive ENaC maintains whole body Na+ homeostasis by modulating Na+ transport via epithelia. This classical role is mostly confirmed using genetically engineered animal models. Recently identified key signaling pathways that regulate ENaC expression and function unveiled some nonclassical and unexpected channel regulatory processes. If aberrant, these dysregulated mechanisms may also result in the development of salt-dependent hypertension.The purpose of this review is to highlight the most recent findings in renal ENaC regulation and function, in considering data obtained from animal models.SummaryIncreased ENaC-mediated Na+ transport is a prerequisite for salt-dependent forms of hypertension. To treat salt-sensitive hypertension it is crucial to fully understand the function and regulation of ENaC.

Tmprss2 maintains epithelial barrier integrity and transepithelial sodium transport

“…ENaC is a transmembrane channel crucial in maintaining sodium balance and fluid homeostasis in various epithelial tissues, such as the kidney, lung, and colon ( Ehret & Hummler, 2022 ). In this study, using the well-established mCCD cl1 cell line, we investigated the relationship between Tmprss2 and ENaC by modulating their expression.…”

“…ENaC is expressed in the tight epithelia of various tissues such as the kidney, colon, lung, and sweat glands; in the kidney, it is localized to the distal convoluted tubule, the connecting tubule, and the cortical collecting duct ( Rotin & Staub, 2021 ). ENaC plays a major role in the regulation of vectorial transcellular sodium transport in the distal part of the nephron, allowing the passive movement of sodium from the tubular lumen towards the blood, and is largely responsible for the fine-tuning of sodium homeostasis ( Ehret & Hummler, 2022 ). Many membrane-bound proteases have been identified as ENaC-activating proteases, also named CAPs (channel-activating proteases) ( Anand et al, 2022 ).…”