Sulfhydryl oxidation induces rapid and reversible closure of the ATP-regulated K+ channel in the pancreatic β-cell

Md Shahidul Islam, Per Olof Berggren, Olof Larsson

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Effects of sulfhydryl modification on the ATP regulated K1 channel (KATP channel) in the pancreatic β-cell were studied, using the patch clamp technique. Application of the sulfhydryl oxidizing agents thimerosal and 2,2'-dithio-bis(5-nitropyridine) (DTBNP), in micromolar concentrations, caused complete inhibition of the kATP channel, in inside-out patches. The inhibition was rapid and was reversed by the disulfide reducing agents dithiothreitol and cysteine. Thimerosal, which is poorly membrane permeable, inhibited channel activity, only when applied to the intracellular face of the plasma membrane. In contrast, DTBNP, which is highly lipophilic, caused closure of the kATP channel and consequent depolarization of the membrane potential, also when applied extracellularly. Our results indicate the presence of accessible free SH groups on the cytoplasmic side of the kATP channel in the pancreatic β-cell. These SH groups are essential for channel function and it is possible that thiol-dependent redox mechanisms can modulate KATP channel activity.

Original languageEnglish
Pages (from-to)128-132
Number of pages5
JournalFEBS Letters
Volume319
Issue number1-2
DOIs
StatePublished - Mar 15 1993
Externally publishedYes

Fingerprint

Thimerosal
KATP Channels
Adenosine Triphosphate
Membranes
Oxidation
Dithiothreitol
Reducing Agents
Depolarization
Clamping devices
Patch-Clamp Techniques
Cell membranes
Sulfhydryl Compounds
Oxidants
Disulfides
Membrane Potentials
Oxidation-Reduction
Cysteine
Cell Membrane
2,2'-dithiobis(5-nitropyridine)

Keywords

  • ATP-regulated K channel
  • Pancreatic β-cell
  • Sulfhydryl reagent
  • Thimerosal

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Sulfhydryl oxidation induces rapid and reversible closure of the ATP-regulated K+ channel in the pancreatic β-cell. / Islam, Md Shahidul; Berggren, Per Olof; Larsson, Olof.

In: FEBS Letters, Vol. 319, No. 1-2, 15.03.1993, p. 128-132.

Research output: Contribution to journalArticle

Islam, Md Shahidul ; Berggren, Per Olof ; Larsson, Olof. / Sulfhydryl oxidation induces rapid and reversible closure of the ATP-regulated K+ channel in the pancreatic β-cell. In: FEBS Letters. 1993 ; Vol. 319, No. 1-2. pp. 128-132.
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