Laboratory of Ion Channels, Biological Membranes and Cell Signaling, Dept. of Biophysics, Facultad de Medicina, CP 11800, Universidad de la Republica, Montevideo, Uruguay.
Laboratory of Ion Channels, Biological Membranes and Cell Signaling, Dept. of Biophysics, Facultad de Medicina, CP 11800, Universidad de la Republica, Montevideo, Uruguay.
Biochim Biophys Acta Mol Basis Dis. 2023 Oct;1869(7):166803. doi: 10.1016/j.bbadis.2023.166803. Epub 2023 Jul 3.
Inwardly rectifying potassium (Kir) channels play a key role in maintaining the resting membrane potential and supporting potassium homeostasis. There are many variants of Kir channels, which are usually tetramers in which the main subunit has two trans-membrane helices attached to two N- and C-terminal cytoplasmic tails with a pore-forming loop in between that contains the selectivity filter. These channels have domains that are strongly modulated by molecules present in nutrients found in different diets, such as phosphoinositols, polyamines and Mg. These molecules can impact these channels directly or indirectly, either allosterically by modulation of enzymes or via the regulation of channel expression. A particular type of these channels is coupled to cell metabolism and inhibited by ATP (KATP channels, essential for insulin release and for the pathogenesis of metabolic diseases like diabetes mellitus). Genomic changes in Kir channels have a significant impact on metabolism, such as conditioning the nutrients and electrolytes that an individual can take. Thus, the nutrigenomics of ion channels is an important emerging field in which we are attempting to understand how nutrients and diets can affect the activity and expression of ion channels and how genomic changes in such channels may be the basis for pathological conditions that limit nutrition and electrolyte intake. In this contribution we briefly review Kir channels, discuss their nutrigenomics, characterize how different components in the diet affect their function and expression, and suggest how their genomic changes lead to pathological phenotypes that affect diet and electrolyte intake.
内向整流钾 (Kir) 通道在维持静息膜电位和支持钾离子稳态方面发挥着关键作用。Kir 通道有许多变体,通常是由四个亚基组成的四聚体,其中主要亚基有两个跨膜螺旋,连接两个 N-和 C-末端细胞质尾部,中间有一个形成孔的环,其中包含选择性过滤器。这些通道的结构域受到不同饮食中存在的营养物质分子的强烈调节,如磷酸肌醇、多胺和 Mg。这些分子可以直接或间接地影响这些通道,通过调节酶的变构作用或通过调节通道表达来实现。这些通道的一种特殊类型与细胞代谢偶联,并被 ATP 抑制(KATP 通道,对于胰岛素释放和代谢疾病如糖尿病的发病机制至关重要)。Kir 通道的基因组变化对代谢有重大影响,例如调节个体可以摄取的营养物质和电解质。因此,离子通道的营养基因组学是一个重要的新兴领域,我们试图理解营养物质和饮食如何影响离子通道的活性和表达,以及这些通道中的基因组变化如何成为限制营养物质和电解质摄入的病理状况的基础。在这篇综述中,我们简要回顾了 Kir 通道,讨论了它们的营养基因组学,描述了饮食中的不同成分如何影响它们的功能和表达,并提出了它们的基因组变化如何导致影响饮食和电解质摄入的病理表型。