A glucocorticoid‐induced Na + conductance in human airway epithelial cells identified by perforated patch recording

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.