Thiol oxidation by 2,2′-dithiodipyridine causes a reversible increase in cytoplasmic free Ca2+ concentration in pancreatic β-cells: Role for inositol 1,4,5-trisphosphate-sensitive Ca2+ stores

Md Shahidul Islam, Henrik Kindmark, Olof Larsson, Per Olof Berggren

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

2,2'-Dithiodipyridine (2,2'-DTDP), a reactive disulphide that mobilizes Ca2+ from ryanodine-sensitive Ca2+ stores in muscle, induced a biphasic increase in cytoplasmic free Ca2+ concentration ([Ca2+](i)) in pancreatic β-cells loaded with fura 2. This increase consisted of an early transient followed by a second, slower, rise. The [Ca2+](i) transient was dependent on extracellular Ca2+ and disappeared on treatment with nimodipine. The reactive disulphide caused plasma membrane depolarization, as studied by the perforated-patch configuration of the patch-clamp technique. Hence membrane depolarization and opening of the L-type voltage-gated Ca2+ channels were responsible for the first transient in [Ca2+](i). The second slower increase in [Ca2+](i) was prolonged but readily reversed by the disulphide-reducing agent 1,4-dithiothreitol. This increase in [Ca2+](i) was not decreased by nimodipine or by omission of extracellular Ca2+, but was eliminated when the Ins(1,4,5)P3-sensitive Ca2+ pool was first depleted by carbachol. Ryanodine or its β-alanyl analogue did not release Ca2+ from intracellular stores, and a high concentration of ryanodine did not inhibit Ca2+ release by 2,2'-DTDP. The disulphide compound suppressed glucose metabolism and decreased the mitochondrial inner-membrane potential. We conclude that thiol oxidation by 2,2'-DTDP affects Ca2+ homeostasis in β-cells by multiple mechanisms. However, unlike the situation in muscle, in β-cells 2,2'-DTDP releases Ca2+ from intracellular pools by mechanisms that do not involve activation of ryanodine receptors. Instead, in these cells the Ins(1,4,5)P3-sensitive intracellular Ca2+ store comprises an alternative target for the Ca2+-mobilizing action of the reactive disulphide compound.

Original languageEnglish (US)
Pages (from-to)347-354
Number of pages8
JournalBiochemical Journal
Volume321
Issue number2
DOIs
StatePublished - Jan 15 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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