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1 Lung Membrane Transport Group, Division of Maternal and Child Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK2 Department of Physiology, University of Otago, Dunedin, New Zealand
The perforated patch recording technique was used to investigate the effects of dexamethasone (0.2 µM, 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 (Vm). 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 Vm 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 Vm 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 (ENa), and replacing Na+ with K+ caused a leftward shift in reversal potential (VRev) that correlated with the corresponding shift in ENa. Lowering [Na+]o to 10 mM, the concentration in the pipette solution, by substitution with NMDG+ shifted VRev 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.
(Received 14 January 2004;
accepted after revision 6 April 2004;
first published online 16 April 2004)
Corresponding author S. M. Wilson: Lung Membrane Transport Group, Division of Maternal and Child Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK. Email: s.m.wilson{at}dundee.ac.uk
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