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Tuesday 15 June 2004

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

By: Clunes MT, Butt AG, Wilson SM.

J Physiol 2004 Jun 15;557(Pt 3):809-19

The perforated patch recording technique was used to investigate the effects of dexamethasone (0.2 microm, 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 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(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 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 approximately 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.

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