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. 2018 Oct 2;5:261. doi: 10.3389/fmed.2018.00261

Figure 3.

Figure 3

In the distal convoluted tubule the final 10% of magnesium is reabsorbed in an active transcellular manner. The tubular epithelium in this part has a lumen-negative voltage. Apical reabsorption occurs via TRPM6, which can be stimulated via the basolateral EGFR. Kv1.1, an apically located potassium channel, establishes a favorable luminal membrane potential facilitating an increase in the driving force for magnesium reabsorption via TRPM6. At the basolateral membrane, magnesium is extruded via an unknown mechanism likely SLC41A1 transporter, which may be regulated by cyclin M2 acting as magnesium sensor. Magnesium extrusion depends on the sodium gradient, set by the Na+-K+-ATPase. The activity of the Na+-K+-ATPase is in turn dependent on potassium recycling via Kir4.1 channel. Tacrolimus and cyclosporine downregulate TRPM6 which is the major active transport protein in the distal tubule that is needed for reabsorption of magnesium. Cyclosporine also decreases the expression of EGF, and hence decreasing the expression of TRPM6. TRPM6, transient receptor potential melastatin type 6; Kv1.1, apical voltage-gated K channel 1.1; NCC, sodium chloride cotransporter; SLC41A1, solute carrier family 41 A1 Mg2+ transporter; Kir4.1, basolateral voltage-gated channel; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor.