Objectives: 

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 epithelial cells.

Materials: 

The expression of H2S-generating enzymes (cystathionine-beta-synthase and cystathionine-gamma-lyase) was investigated on H441 airway epithelial cells by reverse transcriptase PCR and western blot. Ion transport processes were electrophysiologically assessed in Ussing chambers on H441 cells grown on permeable supports at air/liquid interface and on native tracheal preparations of pigs and mice. The effects of H2S were further investigated on Na+ channels expressed in Xenopus oocytes and Na+/K+-ATPase activity in vitro. Membrane abundance of Na+/K+-ATPase was determined by surface biotinylation and western blot. Cellular ATP concentrations were measured colorimetrically, and cytosolic Ca2+ concentrations were measured with Fura-2.

Results: 

Both H2S-generating enzymes were expressed in H441 airway epithelial cells. H2S rapidly and reversibly inhibited Na+ transport in all employed models. There was no effect on Na+ channels, whereas Na+/K+-ATPase currents were decreased. Membrane abundance, metabolic or calcium-dependent regulation, as well as direct activity of the Na+/K+-ATPase, were not involved in the H2S-effects. H2S inhibited basolateral calcium-dependent K+ channels, which consequently decreased Na+ absorption by H441 monolayers.

Conclusions: 

H2S impairs pulmonary transepithelial Na+ absorption, mainly due to the inhibition of basolateral calcium-dependent K+ channels. This data suggests that H2S signaling might represent a novel regulatory system for pulmonary transepithelial Na+ transport.