Fig. 3.

Regulated paracellular Mg²⁺ absorption in the thick ascending limb of Henle (TAL). Claudin-16 by itself is highly permeable to Na⁺, and claudin-19 is impermeable to Cl⁻. Claudin-14 deters the sodium channel permeability of claudin-16. Na⁺ backleaks into the distal part of the TAL and helps in maintaining a positive luminal voltage. Blockage of this action of claudin-14 compromises the positive luminal voltage and diminishes the driving force for Mg²⁺ absorption. The deterrence of Cl⁻ passage by claudin-19 creates a negative microdomain charge, creating a selective attraction to luminal Mg²⁺ and Ca²⁺. The basolateral calcium-sensing receptor (CaSR), when activated by an elevated concentration of Mg²⁺ or Ca²⁺, inhibits miR-9 and miR-375. The inhibition removes the interference of the microRNAs with claudin-14 translation, resulting in an increased claudin-14 translation and claudin-14-mediated inhibition of claudin-16, thus inhibiting Mg²⁺ and Ca²⁺ absorption.