title: The gasotransmitter hydrogen sulphide decreases Na⁺ transport across pulmonary epithelial cells.
abstract: 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.
authors.affiliation: Institute of Animal Physiology, Justus-Liebig University of Giessen, Giessen, Germany. mike.althaus@bio.uni-giessen.de
authors.forename: M
authors.initials: M
authors.lastname: Althaus
authors.forename: K D
authors.initials: KD
authors.lastname: Urness
authors.forename: W G
authors.initials: WG
authors.lastname: Clauss
authors.forename: D L
authors.initials: DL
authors.lastname: Baines
authors.forename: M
authors.initials: M
authors.lastname: Fronius
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D053503:Epithelial Sodium Channels / Q000502:physiology; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D012964:Sodium / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D013552:Swine; D014982:Xenopus laevis
chemical_list: D053503:Epithelial Sodium Channels; D024681:Potassium Channels, Calcium-Activated; D000255:Adenosine Triphosphate; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D006862:Hydrogen Sulfide