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A glucocorticoid‐induced Na + conductance in human airway epithelial cells identified by perforated patch recording
Author(s) -
Clunes M. T.,
Butt A. G.,
Wilson S. M.
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.061143
Subject(s) - amiloride , depolarization , chemistry , hyperpolarization (physics) , membrane potential , conductance , reversal potential , biophysics , patch clamp , stereochemistry , sodium , biochemistry , biology , receptor , mathematics , organic chemistry , combinatorics , nuclear magnetic resonance spectroscopy
The perforated patch recording technique was used to investigate the effects of dexamethasone (0.2 μ m , 24–30 h), a synthetic glucocorticoid, on membrane conductance in the human airway epithelial cell line H441. Under zero current clamp conditions this hormone induced amiloride‐sensitive depolarization of the membrane potential ( V m ). Lowering external Na + to 10 m m by replacing Na + with N ‐methyl‐ d ‐glucammonium (NMDG + ) also hyperpolarized the dexamethasome‐treated cells, whilst replacing Na + with Li + caused a small depolarization. Although V m was insensitive to amiloride in control cells, NMDG + substitution caused a small hyperpolarization and so an amiloride‐insensitive cation conductance is present. Replacing Na + with Li + had no effect on V m in such cells. Voltage clamp studies of dexamethasone‐treated cells showed that the amiloride‐sensitive component of the membrane current reversed at a potential close to the Na + equilibrium potential ( E Na ), and replacing Na + with K + caused a leftward shift in reversal potential ( V Rev ) that correlated with the corresponding shift in E Na . Lowering [Na + ] o to 10 m m , the concentration in the pipette solution, by substitution with NMDG + shifted V Rev to 0 mV, whilst replacing Na + with Li + caused a rightward shift. Exposing dexamethasone‐treated cells to a cocktail of cAMP‐activating compounds (20 min) caused a ∼2‐fold increase in amiloride‐sensitive conductance that was associated with no discernible change in ionic selectivity and an 18 mV depolarization. Dexamethasone thus induces the expression of a selective Na + conductance with a substantial permeability to Li + that is subject to acute regulation via cAMP. These data thus suggest that selective Na + channels underlie cAMP‐regulated Na + transport in airway epithelia.