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

J P Winpenny, A Harris, M A Hollingsworth, B E Argent, M A Gray

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

Using the whole-cell patch-clamp technique, a calcium-activated chloride conductance (CACC) could be elicited in HPAF cells by addition of 1 microM ionomycin to the bath solution (66 +/- 22 pA/pF;Vm + 60 mV) or by addition of 1 microM calcium to the pipette solution (136 +/- 17 pA/pF; Vm + 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 (Erev) close to the calculated chloride equilibrium potential. The anion permeability sequence obtained from shifts in Erev was I > Br >/= Cl. 4,4'-Diisothiocyanatostilbene disulphonic acid (DIDS, 500 microM) caused a 13% inhibition of the current (Vm + 60 mV) while 100 microM glibenclamide, 30 nM TS-TM-calix[4]arene and 10 microM tamoxifen, all chloride channel blockers, had no marked effects (8%, -6% and -2% inhibition respectively). Niflumic acid (100 microM) caused a voltage-dependent inhibition of the current of 48% and 17% (Vm +/- 60 mV, respectively). In freshly isolated human pancreatic duct cells (PDCs) a CACC was elicited with 1 microM calcium in the pipette solution (260 +/- 62 pA/pF; Vm + 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.

Original languageEnglish
Pages (from-to)796-803
Number of pages8
JournalPflügers Archiv: European Journal of Physiology
Volume435
Issue number6
DOIs
Publication statusPublished - May 1998

Keywords

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/pharmacology
  • Action Potentials
  • Adenocarcinoma/physiopathology
  • Anions
  • Calcium/pharmacology
  • Chelating Agents/pharmacology
  • Chloride Channels/analysis
  • Egtazic Acid/pharmacology
  • Electric Conductivity
  • Humans
  • Iodides/metabolism
  • Ionomycin/pharmacology
  • Male
  • Pancreatic Ducts/chemistry
  • Pancreatic Neoplasms/physiopathology
  • Tumor Cells, Cultured

Fingerprint

Dive into the research topics of 'Calcium-activated chloride conductance in a pancreatic adenocarcinoma cell line of ductal origin (HPAF) and in freshly isolated human pancreatic duct cells'. Together they form a unique fingerprint.

Cite this