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 (H2S) 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 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. KEY RESULTS H2S rapidly and reversibly inhibited Na+ transport in all the models employed. H2S had no effect on Na+ channels, whereas it decreased Na+/K+-ATPase currents. H2S did not affect the membrane abundance of Na+/K+-ATPase, its metabolic or calcium-dependent regulation, or its direct activity. However, H2S inhibited basolateral calcium-dependent K+ channels, which consequently decreased Na+ absorption by H441 monolayers. CONCLUSIONS AND IMPLICATIONS H2S impairs pulmonary transepithelial Na+ absorption, mainly by inhibiting basolateral Ca2+-dependent K+ channels. These data suggest that the H2S signalling system might represent a novel pharmacological target for modifying pulmonary transepithelial Na+ transport.