Figure 4.

Proposed mechanism of amiloride inhibition of Mg²⁺ wasting along the late distal convoluted tubule (DCT2). (A) In states of high aldosterone (High Aldo) the apical membrane is depolarized as a result of sodium entry via the ENaC (top panel shows voltage trace). This means that the transepithelial voltage is oriented with the lumen negative, relative to the basal side. The depolarized apical membrane voltage drives little Mg²⁺ into the cell through TRPM6/7, as the membrane voltage across the apical membrane is the primary driving force. The bottom panel shows this schematically. (B) Amiloride treatment inhibits sodium entry through ENaC, eliminating the negative transepithelial potential and hyperpolarizing the apical membrane (top panel shows voltage trace), leading to a net increase in the driving force for Mg²⁺ to enter the cell across the apical membrane through TRPM6/7. The bottom panel shows this schematically. V_TE, transepithelial voltage.