The expression and regulation of depolarization-activated K+ channels in the insulin-secreting cell line INS-1

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Author(s)

  • Jiping Su
  • Huang Yu
  • Nibedita Lenka
  • Jürgen Hescheler
  • Susanne Ullrich

Detail(s)

Original languageEnglish
Pages (from-to)49-56
Journal / PublicationPflugers Archiv European Journal of Physiology
Volume442
Issue number1
Publication statusPublished - 2001
Externally publishedYes

Abstract

The aim of the present study was to characterize depolarization-activated outward currents in insulinsecreting INS-1 cells and to investigate the role of K+ channels other than the KATP channels in the regulation of insulin release. Outward currents were inhibited by 4-aminopyridine (4-AP, 10 mmol/l), tetraethylammonium (TEA, 10 mmol/l) and tetrapentylammonium (TPeA, 100 μmol/l) by 55.1±3.8% (n=3), 78.1±3.2% (n=6) and 98.7±0.8% (n=5), respectively. Margatoxin (5 nmol/l) and charybdotoxin (3 μmol/l) had no effect. 4-AP inhibited mainly a fast-activating, slowly inactivating current, whereas the TEA- and TPeA-sensitive current components were slowly activating and non-inactivating. Forskolin and the forskolin analogue 1,9-dideoxyforskolin, which does not stimulate a denylyl cyclase, also inhibited the outward current, suggesting a direct effect on the channels. Using reverse transcriptase polymerase chain reaction (RT/PCR), Kv channel mRNAs of Kv1.4, Kv1.5, Kv2.1, Kv2.2, Kv3.1 and Kv3.2 were detected whereas other Kv channels; Kv1.1, Kv1.2, Kv1.3, Kv1.6 and Kv3.4 were not detected. Insulin secretion in the presence of tolbutamide (100 μmol/l) was increased by 4-AP, TEA and TPeA by 65%, 41% and 150%, respectively. Basal secretion was not affected by these blockers. Our study reveals that the opening of voltage-dependent K+ channels negatively controls insulin secretion in depolarized cells, probably by shortening the action potential thus reducing Ca2+ influx.

Research Area(s)

  • Action potential regulation, Insulin secretion, K+ channels, Kv channels, Patch-clamp measurements

Bibliographic Note

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