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.
Document Type: | Article |
---|---|
Language: | English |
Author: | M. Althaus, K. D. Urness, W. G. Clauss, D. L. Baines, M. Fronius |
Parent Title (English): | British Journal of Pharmacology |
Volume: | 166 |
Issue: | 6 |
Number of pages: | 18 |
First Page: | 1946 |
Last Page: | 1963 |
ISSN: | 1476-5381 |
DOI: | https://doi.org/10.1111/j.1476-5381.2012.01909.x |
PMID: | https://pubmed.ncbi.nlm.nih.gov/22352810 |
Publisher: | The British Pharmacological Society |
Date of first publication: | 2012/02/21 |
Keyword: | ENaC; Na+/K+-ATPase; lung; sodium absorption; sodium channel |
Departments, institutes and facilities: | Institut für funktionale Gen-Analytik (IFGA) |
Dewey Decimal Classification (DDC): | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Entry in this database: | 2023/03/22 |