Upregulation of sodium conductive pathways in alveolar type II cells in sublethal hyperoxia.

We investigated whether exposure of rats to sublethal hyperoxia (85% O2 for 7 days) raises the levels of proteins antigenically related to Na+ channels in alveolar type II (ATII) cells and, if so, whether this rise was accompanied by an increase in conductive Na+ transport in vitro. ATII cells were isolated from the lungs of these rats at the end of the exposure period. In Western blot studies, a polyclonal antibody raised against Na+ channel protein (NaAb), recognized in a specific manner a 135 +/- 10 kDa polypeptide in plasma membrane vesicles of ATII cells from both control and oxygen-exposed rats. However, higher levels of immunoreactivity were seen in ATII cells from oxygen-exposed rats. When ATII cells were patched in the whole cell mode using symmetrical solutions (150 mM Na(+)-glutamate), outward rectified Na+ currents were observed. When corrected for cell capacitance, both inward and outward currents of ATII cells from rats exposed to hyperoxia were significantly higher than control. Addition of either 1 microM amiloride or 1 microM 5-(N-ethyl-N-isopropyl)-2'-4'-amiloride in the bath solution decreased the magnitude of outward currents of both control and hyperoxic ATII cells by approximately 50%. Taken together, these results indicate that exposure of rats to sublethal hyperoxia results in upregulation of ATII cell conductive pathways with low affinity to amiloride and increased Na+ transport. This may be an early adaptive response that limits the degree of alveolar edema in injured lungs.