Inhibition of Na+ transport in mouse lung exposed to chlorine (Cl2)

Lung fluid balance is finely tuned by vectorial transport of ions across the epithelium. Active sodium reabsorption generates the driving force needed for fluid clearance. In the inflammatory disease of the lung, high levels of Hypochlorus acid (HOCl) are generated by stimulated neutrophils. HOCl causes extensive damage through its reaction with cellular substances such as thiols and amines. In addition to the physiological sources, HOCl can be generated by inhalation of Cl 2 known to induce lung edema. Herein; we investigated the effect of HOCl on ENaC in mouse lungs exposed to 400 ppm Cl 2 , one hour and 24 hours later using the single channel recording on live lung slices. The control alveolar cells exhibited two Na + conductances, highly selective 4–6 pS and moderately selective 14–16 pS. Both were amiloride sensitive. One hour after exposure to Cl 2 , the P o of both channels was significantly reduced from 0.25 ± 0.05 to 0.06 ± 0.01 (p<0.001) and 0.12 ± 0.07 to 0.02 ± 0.005 (p<0.001) for highly and moderately selective channels, respectively. At 24 hours post exposure to Cl 2 the P o of both channels recovered to 50% of its initial value in addition a new non selective conductance of 25 pS was observed. In experiments where animals were exposed to Cl 2 and injected with a cocktail of antioxidants the recovery was faster, both pre‐existing channels recovered by 90% of their initial values. The non selective conductance (25 pS) was less active. Cl 2 gas inhalation inhibits ENaC which may lead to alveolar edema formation. This injury was prevented by post administration of antioxidants. This Research was supported by NIH U01 ES015675 and U54 ES017218 grant to Sadis Matalon.