THE ION CONDUCTANCES OF CFPAC-1 CELLS

The CFPAC-1 cell line was derived from a pancreas duct carcinoma from a patient suffering from DELTAF 508 cystic fibrosis (CF). This cell therefore should be well suited to study the Cl- transport defect in CF. We used slow whole cell (SWC) and cell-attached nystatin (CAN) patch clamp techniques to characterize these cells and we confirm that cAMP fails to induce Cl- currents. Ca2+-mobilizing agents such as neurotensin (NT). ATP, and carbachol all induce a depolarization together with an increase in conductance. This was revealed in SWC and in apical membrane CAN experiments. The half-maximal conductance effect of NT was at 10(-9) mol/l, that of ATP at 10(-6) mol/l. For carbachol, only 10(-4) mol/l was examined. In CAN experiments, no clear current events were detectable in apical membrane patches, suggesting that the Cl- channel responsible for the measured increase in conductance has a conductance too small to be resolved as a single channel event. Hypotonic cell swelling also induced a biphasic voltage response with a predominant increase in Cl- conductance. This effect was detectable in SWC and CAN recordings for 240 mosm/l NaCl and was further enhanced at 160 mosm/l NaCl. The conductance sequence for this and the ATP-induced pathway was I- = Br- = Cl-. Both pathways were inhibited equally well by 10(-3) mol/l DIDS, and they were not additive with respect to their conductance effects. These data indicate that cell swelling as well as Ca2+ mobilization activates a Cl- conductance which consists of the synchronous activity of nondetectable single Cl- currents. These currents appear to be the same as those recently described in HT29 cells.