ANOMALIES IN ION-TRANSPORT IN CF MOUSE TRACHEAL EPITHELIUM

The cystic fibrosis (CF) mouse trachea has become a model for gene tra nsfer. To characterize ion transport properties of tracheal epithelium from normal and CF mice, tracheas were excised, mounted in Ussing cha mbers, and basal properties and responses to pharmacological agents an d/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, nor mal; 13 +/- 2.3 mu A/cm(2), n = 16, CF). Forskolin was observed to inc rease intracellular Ca2+ in both normal and CF tracheal cells, suggest ing 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 f or assessment of CF correction by gene transfer.