Valinsky William C, Touyz Rhian M, Shrier Alvin
Department of Physiology, McGill University, Montreal, QC, Canada.
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
Vitam Horm. 2019;109:105-131. doi: 10.1016/bs.vh.2018.10.004. Epub 2018 Dec 1.
Since its discovery, aldosterone and ion modulation have been entwined. While scientific investigations throughout the decades have emphasized aldosterone's connection to Na, K, and H homeostasis, more recent research has demonstrated a relationship between aldosterone and Mg, Ca, and Cl homeostasis. The mechanisms connecting aldosterone to ion regulation frequently involve ion channels; the membrane localized proteins containing at least one aqueous pore for ion conduction. In order to precisely control intracellular or intraorganelle ion concentrations, ion channels have evolved highly specific regions within the conduction pore that select ions by charge, size, and/or dehydration energy requirement, meaning aldosterone must be able to modulate multiple ion channels to regulate the many ions described above. The list of ion channels presently connected to aldosterone includes ENaC (Na), ROMK/BK (K), TRPV4/5/6 (Ca), TRPM7/6 (Mg), and ClC-K/CFTR (Cl), among others. This list is only expected to grow over time, as the promiscuity of aldosterone becomes more understood.
自醛固酮被发现以来,醛固酮与离子调节就紧密相连。尽管数十年来的科学研究一直强调醛固酮与钠、钾和氢稳态的关联,但最近的研究表明醛固酮与镁、钙和氯稳态之间也存在联系。将醛固酮与离子调节联系起来的机制通常涉及离子通道;这些膜定位蛋白含有至少一个用于离子传导的水性孔道。为了精确控制细胞内或细胞器内的离子浓度,离子通道在传导孔道内进化出了高度特异性的区域,这些区域通过电荷、大小和/或脱水能量需求来选择离子,这意味着醛固酮必须能够调节多个离子通道来调节上述多种离子。目前与醛固酮相关的离子通道包括上皮钠通道(ENaC,钠)、肾髓质外向钾通道/大电导钙激活钾通道(ROMK/BK,钾)、瞬时受体电位香草酸亚型4/5/6(TRPV4/5/6,钙)、瞬时受体电位 melastatin 7/6(TRPM7/6,镁)以及氯通道K/囊性纤维化跨膜传导调节因子(ClC-K/CFTR,氯)等等。随着对醛固酮多效性的理解不断深入,预计这个列表还会随着时间的推移而增加。