The gasotransmitter hydrogen sulphide decreases Na+ transport across pulmonary epithelial cells
M Althaus, KD Urness, WG Clauss… - British journal of …, 2012 - Wiley Online Library
British journal of pharmacology, 2012•Wiley Online Library
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 …
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 …
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.
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