Calcium-activated chloride conductance in a pancreatic adenocarcinoma cell line of ductal origin (HPAF) and in freshly isolated human pancreatic duct cells

Using the whole-cell patch-clamp technique, a calcium-activated chloride conductance (CACC) could be elicited in HPAF cells by addition of 1 μM ionomycin to the bath solution (66 ± 22 pA/pF;V m + 60 mV) or by addition of 1 μM calcium to the pipette solution (136 ± 17 pA/pF; V m + 60 mV). Both conductances had similar biophysical characteristics, including time-dependent inactivation at hyperpolarising potentials and a linear/slightly outwardly rectifying current/voltage (I/V) curve 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 ≥ Cl. 4,4′-Diisothiocyanatostilbene disulphonic acid (DIDS, 500 μM) caused a 13% inhibition of the current (V m + 60 mV) while 100 μM glibenclamide, 30 nM TS-TM-calix[4]arene and 10 μM tamoxifen, all chloride channel blockers, had no marked effects (8%, –6% and –2% inhibition respectively). Niflumic acid (100 μM) caused a voltage-dependent inhibition of the current of 48% and 17% (V m ± 60 mV, respectively). In freshly isolated human pancreatic duct cells (PDCs) a CACC was elicited with 1 μM calcium in the pipette solution (260 ± 62 pA/pF; V m + 60 mV). The presence of this CACC in human PDCs could provide a possible therapeutic pathway for treatment of pancreatic insufficiency of the human pancreas in cystic fibrosis.