INCREASED EXPRESSION AND ACTIVITY OF SODIUM-CHANNELS IN ALVEOLAR TYPE-II CELLS OF HYPEROXIC RATS

We investigated the cellular and molecular events associated with the increase in sodium transport across the alveolar epithelium of rats exposed to hyperoxia (85% O-2 for 7 days followed by 100% O-2 for 4 days), Alveolar type II (ATII) cell RNA was isolated and probed with a cDNA for one of the rat colonic epithelial sodium channel subunits (alpha rENaC), The alpha rENaC mRNA 3.7-kb transcript) increased 3-fold in ATII cell RNA isolated from rats exposed to 85% O-2 for 7 days and 6-fold after 4 days of subsequent exposure to 100% O-2. In situ hybridization revealed increased expression of alpha rENaC mRNA transcripts in both airway and alveolar epithelial cells of hyperoxic rats, When immunostained with a polyclonal antibody to kidney sodium channel protein, ATII cells from hyperoxic rats exhibited a significant increase in the amount of immunogenic protein present in both the plasma membrane and the cytoplasm, When patched in the whole-cell mode, ATII cells from hyperoxic rats exhibited amiloride and 5-(N-ethyl-N-isopropyl)-2',4'-amiloride (EIPA)sensitive currents that were 100% higher compared with those obtained from air-breathing rats, Single-channel sodium currents (mean conductance of 25 pS) were seen in ATII cells patched in both the inside-out and cell-attached modes, The number and open probability of these channels increased significantly during exposure to hyperoxia, Exposure to sublethal hyperoxia up-regulated both (alpha rENaC mRNA and the functional expression of sodium channels in ATII cells.