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The gasotransmitter hydrogen sulphide decreases Na + transport across pulmonary epithelial cells
Author(s) -
Althaus M,
Urness KD,
Clauss WG,
Baines DL,
Fronius M
Publication year - 2012
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2012.01909.x
Subject(s) - ion transporter , chemistry , transepithelial potential difference , biophysics , ussing chamber , apical membrane , absorption (acoustics) , biochemistry , membrane , biology , in vitro , physics , acoustics
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.