Schematic model of autocrine P2X₄ activation by vesicular ATP. P2X₄ is expressed on the limiting membrane of LBs, and ATP (green) is loaded into LBs by VNUT. The low pH within LBs protects P2X₄ from premature activation. Upon exocytosis and opening of the fusion pore, the pH within the lumen of the fused LB rises and P2X₄ receptors are activated by ATP, resulting in “fusion-activated Ca²⁺-entry” (FACE) at the site of LB fusion. FACE then facilitates fusion pore dilation, surfactant secretion, and fluid resorption from alveoli.