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Magnesium reabsorption in the kidney.

Jeroen H F de Baaij
Published in: American journal of physiology. Renal physiology (2023)
Mg 2+ is essential for many cellular and physiological processes, including muscle contraction, neuronal activity, and metabolism. Consequently, the blood Mg 2+ concentration is tightly regulated by balanced intestinal Mg 2+ absorption, renal Mg 2+ excretion, and Mg 2+ storage in bone and soft tissues. In recent years, the development of novel transgenic animal models and identification of Mendelian disorders has advanced our current insight in the molecular mechanisms of Mg 2+ reabsorption in the kidney. In the proximal tubule, Mg 2+ reabsorption is dependent on paracellular permeability by claudin-2/12. In the thick ascending limb of Henle's loop, the claudin-16/19 complex provides a cation-selective pore for paracellular Mg 2+ reabsorption. The paracellular Mg 2+ reabsorption in this segment is regulated by the Ca 2+ -sensing receptor, parathyroid hormone, and mechanistic target of rapamycin (mTOR) signaling. In the distal convoluted tubule, the fine tuning of Mg 2+ reabsorption takes place by transcellular Mg 2+ reabsorption via transient receptor potential melastatin-like types 6 and 7 (TRPM6/TRPM7) divalent cation channels. Activity of TRPM6/TRPM7 is dependent on hormonal regulation, metabolic activity, and interacting proteins. Basolateral Mg 2+ extrusion is still poorly understood but is probably dependent on the Na + gradient. Cyclin M2 and SLC41A3 are the main candidates to act as Na + /Mg 2+ exchangers. Consequently, disturbances of basolateral Na + /K + transport indirectly result in impaired renal Mg 2+ reabsorption in the distal convoluted tubule. Altogether, this review aims to provide an overview of the molecular mechanisms of Mg 2+ reabsorption in the kidney, specifically focusing on transgenic mouse models and human hereditary diseases.
Keyphrases
  • endothelial cells
  • gene expression
  • mouse model
  • metabolic syndrome
  • coronary artery
  • air pollution
  • skeletal muscle
  • pulmonary hypertension
  • pulmonary artery
  • climate change
  • bone loss
  • human health
  • soft tissue