The gasotransmitter hydrogen sulphide decreases Na + transport across pulmonary epithelial cells

BACKGROUND AND PURPOSE The transepithelial absorption of Na + in the lungs is crucial for the maintenance of the volume and composition of epithelial lining fluid. The regulation of Na + transport is essential, because hypo‐ or hyperabsorption of Na + is associated with lung diseases such as pulmonary oedema or cystic fibrosis. This study investigated the effects of the gaseous signalling molecule hydrogen sulphide (H 2 S) on Na + absorption across pulmonary epithelial cells. EXPERIMENTAL APPROACH 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 H 2 S 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 Ca 2+ concentrations were measured with Fura‐2. KEY RESULTS H 2 S rapidly and reversibly inhibited Na + transport in all the models employed. H 2 S had no effect on Na + channels, whereas it decreased Na + /K + ‐ATPase currents. H 2 S did not affect the membrane abundance of Na + /K + ‐ATPase, its metabolic or calcium‐dependent regulation, or its direct activity. However, H 2 S inhibited basolateral calcium‐dependent K + channels, which consequently decreased Na + absorption by H441 monolayers. CONCLUSIONS AND IMPLICATIONS H 2 S impairs pulmonary transepithelial Na + absorption, mainly by inhibiting basolateral Ca 2+ ‐dependent K + channels. These data suggest that the H 2 S signalling system might represent a novel pharmacological target for modifying pulmonary transepithelial Na + transport.