Department of Physiology, McGill University, 3649 Promenade Sir William Osler, Montreal, Quebec H3G 0B1, Canada.
Institute of Cardiovascular and Medical Sciences, University of Glasgow, BHF GCRC, 126 University Place, Glasgow G12 8TA, U.K.
Clin Sci (Lond). 2018 Jan 19;132(2):173-183. doi: 10.1042/CS20171525. Print 2018 Jan 31.
Hyperaldosteronism, a common cause of hypertension, is strongly connected to Na, K, and Mg dysregulation. Owing to its steroidal structure, aldosterone is an active transcriptional modifier when bound to the mineralocorticoid receptor (MR) in cells expressing the enzyme 11β-hydroxysteroid dehydrogenase 2, such as those comprising the aldosterone-sensitive distal nephron (ASDN). One such up-regulated protein, the ubiquitous serum and glucocorticoid regulated kinase 1 (SGK1), has the capacity to modulate the surface expression and function of many classes of renal ion channels, including those that transport Na (ENaC), K (ROMK/BK), Ca (TRPV4/5/6), Mg (TRPM7/6), and Cl (ClC-K, CFTR). Here, we discuss the mechanisms by which ASDN expressed channels are up-regulated by SGK1, while highlighting newly discovered pathways connecting aldosterone to nonselective cation channels that are permeable to Mg (TRPM7) or Ca (TRPV4).
原发性醛固酮增多症是高血压的常见病因，与钠、钾和镁的失调密切相关。由于其甾体结构，醛固酮在与细胞中表达的 11β-羟甾类脱氢酶 2 的盐皮质激素受体 (MR) 结合时，是一种活跃的转录修饰物，如包含醛固酮敏感的远曲小管 (ASDN) 的那些细胞。上调的一种蛋白，普遍存在的血清和糖皮质激素调节激酶 1 (SGK1)，具有调节许多类肾脏离子通道的表面表达和功能的能力，包括那些运输钠 (ENaC)、钾 (ROMK/BK)、钙 (TRPV4/5/6)、镁 (TRPM7/6) 和氯 (ClC-K、CFTR) 的通道。在这里，我们讨论了由 SGK1 上调 ASDN 表达的通道的机制，同时强调了新发现的连接醛固酮与非选择性阳离子通道的途径，这些通道对镁 (TRPM7) 或钙 (TRPV4) 具有通透性。
