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

40 Scopus citations

Abstract

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 chloride 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.

Original languageEnglish (US)
Pages (from-to)796-803
Number of pages8
JournalPflugers Archiv European Journal of Physiology
Volume435
Issue number6
DOIs
StatePublished - 1998

Keywords

  • Chloride channels
  • Cystic fibrosis
  • HPAF
  • Pancreas
  • Pharmacology

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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