Volume-activated chloride currents in pancreatic duct cells

B Verdon, J P Winpenny, K J Whitfield, B E Argent, M A Gray

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56 Citations (Scopus)

Abstract

We have used the patch clamp technique to study volume-activated Cl- currents in the bicarbonate-secreting pancreatic duct cell. These currents could be elicited by a hypertonic pipette solution (osmotic gradient 20 mOsm/l), developed over about 8 min to a peak value of 91 +/- 5.8 pA/pF at 60 mV (n = 123), and were inhibited by a hypertonic bath solution. The proportion of cells which developed currents increased from 15% in freshly isolated ducts to 93% if the ducts were cultured for 2 days. The currents were ATP-dependent, had an outwardly rectifying current/voltage (I-V) plot, and displayed time-dependent inactivation at depolarizing potentials. The anion selectivity sequence was: ClO4 = I = SCN > Br = NO3 > Cl > F > HCO3 > gluconate, and the currents were inhibited to a variable extent by DIDS, NPPB, dideoxyforskolin, tamoxifen, verapamil and quinine. Increasing the intracellular Ca2+ buffering capacity, or lowering the extracellular Ca2+ concentration, reduced the proportion of duct cells which developed currents. However, removal of extracellular Ca2+ once the currents had developed was without effect. Inhibiting protein kinase C (PKC) with either the pseudosubstrate PKC (19-36), calphostin C or staurosporine completely blocked development of the currents. We speculate that cell swelling causes Ca2+ influx which activates PKC which in turn either phosphorylates the Cl- channel or a regulatory protein leading to channel activation.

Original languageEnglish
Pages (from-to)173-83
Number of pages11
JournalJournal of Membrane Biology
Volume147
Issue number2
DOIs
Publication statusPublished - Sept 1995

Keywords

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/pharmacology
  • Adenosine Triphosphate/metabolism
  • Animals
  • Anions/pharmacology
  • Calcium/metabolism
  • Cell Size
  • Chloride Channels/antagonists & inhibitors
  • Chlorides/metabolism
  • In Vitro Techniques
  • Ion Transport
  • Membrane Potentials
  • Pancreatic Ducts/cytology
  • Phosphorylation
  • Protein Kinase C/antagonists & inhibitors
  • Rats
  • Rats, Wistar

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