Neurobiology Division, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge, UK.
Department of Biology, KU Leuven, Leuven, Belgium.
J Physiol. 2023 May;601(9):1521-1542. doi: 10.1113/JP283335. Epub 2022 Nov 13.
The DEG/ENaC family of ion channels was defined based on the sequence similarity between degenerins (DEG) from the nematode Caenorhabditis elegans and subunits of the mammalian epithelial sodium channel (ENaC), and also includes a diverse array of non-voltage-gated cation channels from across animal phyla, including the mammalian acid-sensing ion channels (ASICs) and Drosophila pickpockets. ENaCs and ASICs have wide ranging medical importance; for example, ENaCs play an important role in respiratory and renal function, and ASICs in ischaemia and inflammatory pain, as well as being implicated in memory and learning. Electrophysiological approaches, both in vitro and in vivo, have played an essential role in establishing the physiological properties of this diverse family, identifying an array of modulators and implicating them in an extensive range of cellular functions, including mechanosensation, acid sensation and synaptic modulation. Likewise, genetic studies in both invertebrates and vertebrates have played an important role in linking our understanding of channel properties to function at the cellular and whole animal/behavioural level. Drawing together genetic and physiological evidence is essential to furthering our understanding of the precise cellular roles of DEG/ENaC channels, with the diversity among family members allowing comparative physiological studies to dissect the molecular basis of these diverse functions.
离子通道的 DEG/ENaC 家族是根据线虫秀丽隐杆线虫中的 DEG（退行基因）与哺乳动物上皮钠通道（ENaC）亚基之间的序列相似性来定义的，它还包括来自动物门的各种非电压门控阳离子通道，包括哺乳动物酸感应离子通道（ASICs）和果蝇 pickpockets。ENaC 和 ASICs 具有广泛的医学重要性；例如，ENaC 在呼吸和肾功能中起着重要作用，ASICs 在缺血和炎症性疼痛中起作用，并且与记忆和学习有关。无论是在体外还是体内，电生理学方法都在确定这个多样化家族的生理特性方面发挥了重要作用，确定了一系列调节剂，并将其与广泛的细胞功能联系起来，包括机械感觉、酸感觉和突触调节。同样，无脊椎动物和脊椎动物的遗传研究在将我们对通道特性的理解与细胞和整体动物/行为水平的功能联系起来方面也发挥了重要作用。将遗传和生理证据结合起来对于进一步了解 DEG/ENaC 通道的精确细胞作用至关重要，家族成员的多样性允许进行比较生理研究，以剖析这些不同功能的分子基础。
