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- W3038202479 abstract "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 Mg2+ reabsorption is tightly regulated. Apical uptake via TRPM6 Mg2+ channels and basolateral Mg2+ extrusion via a putative Na+-Mg2+ exchanger determines Mg2+ 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 Mg2+ 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 Mg2+ 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 Mg2+ 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+-Mg2+ exchanger SLC41A1. Elucidating the interconnections between Mg2+ and Na+ transport in the distal convoluted tubule is hampered by the currently available models. Our analysis indicates that the coupling of Na+ and Mg2+ reabsorption may be multifactorial and that advanced experimental models are required to study the molecular mechanisms." @default.
- W3038202479 created "2020-07-10" @default.
- W3038202479 creator A5014971956 @default.
- W3038202479 creator A5043204023 @default.
- W3038202479 creator A5046600218 @default.
- W3038202479 creator A5084777052 @default.
- W3038202479 date "2020-07-26" @default.
- W3038202479 modified "2023-10-06" @default.
- W3038202479 title "Mechanisms coupling sodium and magnesium reabsorption in the distal convoluted tubule of the kidney" @default.
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