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

M. T. Clunes, A. G. Butt, S. M. Wilson

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    21 Citations (Scopus)

    Abstract

    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.
    Original languageEnglish
    Pages (from-to)809-819
    Number of pages11
    JournalJournal of Physiology
    Volume557
    Issue number3
    DOIs
    Publication statusPublished - 2004

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