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, Michael A Hollingsworth, B. E. Argent, M. A. Gray

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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
Publication statusPublished - May 7 1998

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Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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