Mg2+ transport in the kidney

Magnesium is abundant in biological systems and an important divalent cation in the human body. Mg²⁺ helps mediate cellular energy metabolism, ribosomal and membrane integrity. Additionally Mg²⁺ modulates the activity of several membrane transport and signal transduction systems. Despite its importance however, little is known about the molecular mechanisms of Mg²⁺ transport and homeostasis in mammals. In mammals the amount of Mg²⁺ absorption is about the same as the amount of Mg²⁺ excretion in urine. Additionally, when total Mg²⁺ intake is deficient, the kidney is capable of reabsorbing all filtered Mg²⁺. This balance between intake and excretion indicates that the kidney plays a principal role in maintenance of total body Mg²⁺ homeostasis. Within the kidney, Mg²⁺ filtered by the glomerulus is handled in different ways along the nephron. About 10–20% of Mg²⁺ is reabsorbed by the proximal tubule. the bulk of Mg²⁺ (about 50–70%) is reabsorbed by the cortical thick ascending limb of the loop of Henle. In this region, Mg²⁺ moves across the epithelium through the paracellular pathway, driven by the positive lumenal transepithelial voltage. A recently cloned human gene, paracellin-1 was shown to encode a protein localized to the tight junctions of the cortical thick ascending limb and is thought to mediate Mg²⁺ transport via the paracellular space of this epithelium. The distal convoluted tubule reabsorbs the remaining 5–10% of filtered Mg²⁺. This segment seems to play an important role in determining final urinary excretion, since there is no evidence for significant Mg²⁺ absorption beyond the distal tubule. Although many renal Mg²⁺ transport activities have been characterized, no Mg²⁺ transporter cDNAs have been cloned from mammalian tissues. Recent research has certainly expanded our knowledge of Mg²⁺ transport in kidney; but details of the transport processes and the mechanisms by which they control Mg²⁺ excretion must await cloning of renal Mg²⁺ transporters and/or channels. Such information would provide new concepts in our understanding of renal Mg²⁺ handling.