Bosman Willem, Hoenderop Joost G J, de Baaij Jeroen H F
Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Proc Nutr Soc. 2021 Aug;80(3):327-338. doi: 10.1017/S0029665121000926. Epub 2021 Apr 28.
Magnesium (Mg2+) plays an essential role in many biological processes. Mg2+ deficiency is therefore associated with a wide range of clinical effects including muscle cramps, fatigue, seizures and arrhythmias. To maintain sufficient Mg2+ levels, (re)absorption of Mg2+ in the intestine and kidney is tightly regulated. Genetic defects that disturb Mg2+ uptake pathways, as well as drugs interfering with Mg2+ (re)absorption cause hypomagnesemia. The aim of this review is to provide an overview of the molecular mechanisms underlying genetic and drug-induced Mg2+ deficiencies. This leads to the identification of four main mechanisms that are affected by hypomagnesemia-causing mutations or drugs: luminal transient receptor potential melastatin type 6/7-mediated Mg2+ uptake, paracellular Mg2+ reabsorption in the thick ascending limb of Henle's loop, structural integrity of the distal convoluted tubule and Na+-dependent Mg2+ extrusion driven by the Na+/K+-ATPase. Our analysis demonstrates that genetic and drug-induced causes of hypomagnesemia share common molecular mechanisms. Targeting these shared pathways can lead to novel treatment options for patients with hypomagnesemia.
镁离子（Mg2+）在许多生物过程中发挥着至关重要的作用。因此，Mg2+缺乏与多种临床症状相关，包括肌肉痉挛、疲劳、癫痫发作和心律失常。为维持足够的Mg2+水平，肠道和肾脏对Mg2+的（再）吸收受到严格调控。干扰Mg2+摄取途径的遗传缺陷以及干扰Mg2+（再）吸收的药物会导致低镁血症。本综述的目的是概述遗传和药物诱导的Mg2+缺乏背后的分子机制。这导致确定了受导致低镁血症的突变或药物影响的四种主要机制：管腔瞬时受体电位香草酸亚型6/7介导的Mg2+摄取、亨氏袢升支粗段的细胞旁Mg2+重吸收、远曲小管的结构完整性以及由Na+/K+-ATP酶驱动的Na+依赖性Mg2+排出。我们的分析表明，遗传和药物诱导的低镁血症病因具有共同的分子机制。针对这些共同途径可为低镁血症患者带来新的治疗选择。
