Pflügers Archiv

, Volume 431, Issue 3, pp 363–370 | Cite as

A volume-activated anion conductance in insulin-secreting cells

  • L. Best
  • E. A. Sheader
  • P. D. Brown
Original Article

Abstract

The whole-cell patch-clamp recording technique was used to measure volume-activated currents in K+-free solutions in RINm5F and HIT-T15 insulinoma cells and in dispersed rat islet cells. Cell swelling, induced by intracellular hypertonicity or extracellular hypotonicity, caused activation of an outwardly rectifying conductance which could be subsequently inactivated by hypertonic extracellular solutions. The conductance required adenosine 5′-triphosphate (ATP) in the pipette solution but was Ca2+ independent. Na+ and Cl substitution studies suggested that the swelling-activated current is Cl selective with a halide permeability sequence of Br > Cl > 1. The conductance was reversibly inhibited by the anion channel inhibitors 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS) and by 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB). Further evidence for a volume-activated anion conductance was provided by studies of volume regulation in insulin-secreting cells. When RINm5F cells were exposed to a hypotonic medium, the initial cell swelling was followed by a regulatory volume decrease (RVD). This RVD response was also inhibited by DIDS and by NPPB. These data therefore provide evidence for a volume-activated anion conductance in insulin-secreting cells which could be involved in the RVD following osmotic stress. A possible role for the conductance in hypotonically induced insulin release is also discussed.

Key words

Outwardly rectifying Chloride channel Regulatory volume decrease Pancreaticβ-cell 

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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • L. Best
    • 1
  • E. A. Sheader
    • 1
  • P. D. Brown
    • 1
  1. 1.Cell Physiology Group, School of Biological SciencesUniversity of ManchesterManchesterUK

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