Question: 

The transepithelial absorption of Na⁺ in the lung is crucial for the maintenance of the volume and composition of epithelial lining fluid. The regulation of Na⁺ transport is essential, since hypo- or hyperabsorption of Na⁺ is associated with lung diseases such as pulmonary oedema or cystic fibrosis. This study investigated the effects of the novel gaseous signalling molecule hydrogen sulphide (H₂S) on Na⁺ absorption across pulmonary epithelia.

Methodology: 

Transepithelial ion transport across human H441 cells and native preparations of pig and mouse tracheae was investigated in Usssing chambers. H₂S was applied using the donor molecule NaHS. Membrane abundance of transport molecules was measured by surface biotinylation and western blot. Cytosolic ATP concentrations and the activity of purified Na⁺/K⁺-ATPase were determined colorimetrically.

Results: 

NaHS (300 mM) rapidly and reversibly inhibited amiloride-sensitive Na⁺ transport by 60% in all employed models. There was no effect on Na⁺ channels, whereas Na⁺/K⁺-ATPase currents were decreased. Membrane abundance of the Na⁺/K⁺-ATPase and the activity of purified Na⁺/K⁺-ATPase was not affected by NaHS. There was no effect on cellular ATP concentrations or calcium/protein kinase signalling pathways. NaHS inhibited basolateral K⁺ channels, the inhibition of which decreased Na⁺/K⁺-ATPase currents and Na⁺ absorption by H441 cells.

Conclusion: 

H₂S impairs pulmonary transepithelial Na⁺ absorption by inhibition of basolateral K⁺ channels, which indirectly impairs Na⁺/K⁺-ATPase activity and thus transepithelial Na⁺ transport. These data suggest that the H₂S signalling system might represent a novel pharmacological target for interference with pulmonary transepithelial Na⁺ transport. Funded by DFG AL1453/1-1.