CALCIUM-ACTIVATED CHLORIDE CONDUCTANCE IN A PANCREATIC ADENOCARCINOMACELL-LINE OF DUCTAL ORIGIN (HPAF) AND IN FRESHLY ISOLATED HUMAN PANCREATIC DUCT CELLS

Using the whole-cell patch-clamp technique, a calcium-activated chlori de conductance (CACC) could be elicited in HPAF cells by addition of 1 mu M ionomycin to the bath solution (66 +/- 22 pA/pF:V-m + 60 mV) or by addition of 1 mu M calcium to the pipette solution (136 +/- 17 pA/p F; V-m + 60 mV). Both conductances had similar biophysical characteris tics, including time-dependent inactivation at hyperpolarising potenti als and a linear/slightly outwardly rectifying current/voltage (I/V) c urve with a reversal potential (E-rev) close to the calculated cloride equilibrium potential. The anion permeability sequence obtained from shifts in E-rev was I > Br greater than or equal to Cl. 4,4'-Diisothio cyanatostilbene disulphonic acid (DIDS, 500 mu M) caused a 13% inhibit ion of the current (V-m + 60 mV) while 100 mu M glibenclamide, 30 nM T S-TM-calix[4]arene and 10 mu M tamoxifen, all chloride channel blocker s, had no marked effects (8%, -6% and -2% inhibition respectively). Ni flumic acid (100 mu M) caused a voltage-dependent inhibition of the cu rrent of 48% and 17% (V-m +/- 60 mV, respectively). In freshly isolate d human pancreatic duct cells (PDCs) a CACC was elicited with 1 mu M c alcium in the pipette solution (260 +/- 62 pA/pF; V-m + 60 mV). The pr esence of this CACC in human PDCs could provide a possible therapeutic pathway for treatment of pancreatic insufficiency of the human pancre as in cystic fibrosis.