Mechanisms coupling sodium and magnesium reabsorption in the distal convoluted tubule of the kidney.
SourceActa Physiologica, 231, 2, (2021), article e13528
Article / Letter to editor
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SubjectRadboudumc 11: Renal disorders RIMLS: Radboud Institute for Molecular Life Sciences
Hypomagnesaemia is a common feature of renal Na(+) wasting disorders such as Gitelman and EAST/SeSAME syndrome. These genetic defects specifically affect Na(+) reabsorption in the distal convoluted tubule, where Mg(2+) reabsorption is tightly regulated. Apical uptake via TRPM6 Mg(2+) channels and basolateral Mg(2+) extrusion via a putative Na(+) -Mg(2+) exchanger determines Mg(2+) reabsorption in the distal convoluted tubule. However, the mechanisms that explain the high incidence of hypomagnesaemia in patients with Na(+) wasting disorders of the distal convoluted tubule are largely unknown. In this review, we describe three potential mechanisms by which Mg(2+) reabsorption in the distal convoluted tubule is linked to Na(+) reabsorption. First, decreased activity of the thiazide-sensitive Na(+) /Cl(-) cotransporter (NCC) results in shortening of the segment, reducing the Mg(2+) reabsorption capacity. Second, the activity of TRPM6 and NCC are determined by common regulatory pathways. Secondary effects of NCC dysregulation such as hormonal imbalance, therefore, might disturb TRPM6 expression. Third, the basolateral membrane potential, maintained by the K(+) permeability and Na(+) -K(+) -ATPase activity, provides the driving force for Na(+) and Mg(2+) extrusion. Depolarisation of the basolateral membrane potential in Na(+) wasting disorders of the distal convoluted tubule may therefore lead to reduced activity of the putative Na(+) -Mg(2+) exchanger SLC41A1. Elucidating the interconnections between Mg(2+) and Na(+) transport in the distal convoluted tubule is hampered by the currently available models. Our analysis indicates that the coupling of Na(+) and Mg(2+) reabsorption may be multifactorial and that advanced experimental models are required to study the molecular mechanisms.
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