ANOMALIES IN ION-TRANSPORT IN CF MOUSE TRACHEAL EPITHELIUM

The cystic fibrosis (CF) mouse trachea has become a model for gene transfer. To characterize ion transport properties of tracheal epithelium from normal and CF mice, tracheas were excised, mounted in Ussing chambers, and basal properties and responses to pharmacological agents and/or ion substitution protocols measured. No difference in basal short-circuit current (I-sc) was observed between normal (29.1 +/- 3.8 mu A/cm(2), n = 21) and CF (34.7 +/- 4.5 mu A/cm(2), n = 16) tracheas. The relative contribution of Na+ transport to basal I-sc was small (30-40%). Ionomycin stimulated large increases in I-sc in both normal and CF murine tracheas [change in I-sc (Delta I-sc) with ionomycin: 30.5 +/- 8.8 mu A/cm(2), n = 11, normal; 27.3 +/- 6.7 mu A/cm(2), n = 6, CF]. Unexpectedly, forskolin increased I-sc in both CF and normal amiloride-pretreated tracheas (Delta I-sc: 10.5 +/- 2.1 mu A/cm(2), n = 21, normal; 13 +/- 2.3 mu A/cm(2), n = 16, CF). Forskolin was observed to increase intracellular Ca2+ in both normal and CF tracheal cells, suggesting this as a mechanism to induce Cl- secretion. These similarities in ion transport, in part reflecting the dominance of Ca2+-regulated Cl- conductance, suggest that the murine trachea is not an ideal target for assessment of CF correction by gene transfer.