FIGURE 6.

Pendrin gene ablation modulates luminal ATP concentration, which changes epithelial Na⁺ channel (ENaC) abundance and function. With pendrin gene ablation, H⁺-ATPase abundance falls in the type B intercalated cell, thereby increasing intercalated cell ATP content. Luminal ATP concentration then rises through enhanced connexin 30-mediated ATP secretion. Luminal ATP acts on apical membrane purinergic receptors to stimulate calcium release, which increases prostaglandin E₂ production (PGE₂). PGE₂ acts through a receptor-mediated process to reduce ENaC abundance and function.