Evidence for voltage-activated, dihydropyrjdinesensmve, nonselective cation channels in isolated airway epithelial cells

Mechanical stimulation of trachéal airway epithelial cells may activate voltage-sensitive, dihydropyridine(DHP)-sensitive, Ca2+ conductive ion channels (Boitano, Woodruff and Dirksen, 1995). We have measured whole cell currents by patch clamping isolated ciliated epithelial cells from rabbit trachea to directly assay ionic conductance. With a bath solution of 40 mM BaCl2, 100 mM TEA" C1", 1 mM MgCl2 and an internal solution of primarily cesium methylsulfonate, we observe a depolarizationdependent outward current between 50 and 200 pA. The current is also observed when CT in the bath is replaced by methyl-sulfonate, suggesting that it is primarily due to outward Cs+ current. Voltage-sensitive inward tail currents suggest that Ba2 can be a charge carrier through this channel. The currents are blocked by Cd2 (1 mM) and enhanced by DHP Ca2channel agonist Bay K 8644 (3 JiM). We are attempting to measure the sensitivity of this channel to DHP antagonists and the sensitivity of the current to mechanical stimulation. Stimulus-dependent Ca2+ influx may play an important role in regulation of salt and fluid transport, regulation of ciliary beat frequency and secretory functions of the airway epithelia. This research is supported by the Tobacco Related Disease Research Program of the University of California and NASA Microgravity Research. S.B. is a Parker B. Francis Fellow.