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 mum, 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.). Lowering external Na+ to 10 mm 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-rn 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 damp 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+] 0 to 10 mm, 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 similar to2-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.