The conquest of freshwater and terrestrial habitats was a key event during vertebrate evolution. Occupation of low-salinity and dry environments required significant osmoregulatory adaptations enabling stable ion and water homeostasis. Sodium is one of the most important ions within the extracellular liquid of vertebrates and molecular machinery for urinary reabsorption of this electrolyte is critical for the maintenance of body osmoregulation. Key ion channels involved in the fine-tuning of sodium homeostasis in tetrapod vertebrates are epithelial sodium channels (ENaC) which allow the selective influx of sodium ions across the apical membrane of epithelial cells lining the distal nephron or the colon. Furthermore, ENaC-mediated sodium absorption across tetrapod lung epithelia is crucial for the control of liquid volumes lining the pulmonary surfaces. ENaCs are vertebrate-specific members of the degenerin/ENaC family of cation channels, however, there is limited knowledge in the evolution of ENaC within this ion channel family. This review outlines current concepts and hypotheses on ENaC phylogeny and discusses the emergence of regulation-defining sequence motifs in the context of osmoregulatory adaptations during tetrapod terrestrialisation. Based on the distinct regulation and expression of ENaC isoforms in tetrapod vertebrates we discuss the potential significance of ENaC orthologs in osmoregulation of fish as well as the putative fates of atypical channel isoforms in mammals. We hypothesize that ancestral proton-sensitive ENaC orthologs might have aided the osmoregulatory adaptation to freshwater environments whereas channel regulation by proteases evolved as a molecular adaptation to lung liquid homeostasis in terrestrial tetrapods.

中文翻译：

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上皮钠通道的演变：当前的概念和假设。

在脊椎动物进化过程中，征服淡水和陆地生境是一个关键事件。在低盐度和干燥的环境中需要进行渗透压调节，以实现稳定的离子和水动态平衡。钠是脊椎动物细胞外液中最重要的离子之一，尿液重新吸收这种电解质的分子机制对于维持人体渗透调节至关重要。在四足动物脊椎动物中，钠稳态的微调涉及的关键离子通道是上皮钠通道（ENaC），该通道允许钠离子选择性地流入远端肾单位或结肠内壁的上皮细胞的顶膜。此外，ENaC介导的跨四足动物肺上皮细胞的钠吸收对于控制位于肺表面的液体体积至关重要。ENaCs是简并蛋白/ ENaC阳离子通道家族的脊椎动物特有成员，但是，在该离子通道家族中对ENaC的进化知之甚少。这篇综述概述了有关ENaC系统发育的当前概念和假设，并讨论了在四足动物陆生化过程中渗透调节适应性的背景下，调控定义序列基序的出现。基于四足动物脊椎动物中ENaC亚型的独特调控和表达，我们讨论了ENaC直向同源物在鱼类渗透压调节中的潜在意义以及在哺乳动物中非典型通道亚型的假定命运。